Time Course Of Development Research Articles

Experience-dependent development of perineuronal nets and chondroitin sulfate proteoglycan receptors in mouse visual cortex

Perineuronal nets (PNNs) are extracellular matrix structures consisting of chondroitin sulfate proteoglycans (CSPGs), hyaluronan, link proteins and tenascin-R (Tn-R). They enwrap a subset of GABAergic inhibitory interneurons in the cerebral cortex and restrict experience-dependent cortical plasticity. While the expression profile of PNN components has been widely studied in many areas of the central nervous system of various animal species, it remains unclear how these components are expressed during the postnatal development of mouse primary visual cortex (V1). In the present study, we characterized the developmental time course of the formation of PNNs in the mouse primary visual cortex, using the specific antibodies against the two PNN component proteins aggrecan and tenascin-R, or the lectin Wisteria floribunda agglutinin (WFA) that directly binds to glycosaminoglycan chains of chondroitin sulfate proteoglycans (CSPGs). We found that the fluorescence staining signals of both the WFA staining and the antibody against aggrecan rapidly increased in cortical neurons across layers 2–6 during postnatal days (PD) 10–28 and reached a plateau around PD42, suggesting a full construction of PNNs by the end of the critical period. Co-staining with antibodies to Ca2+ binding protein parvalbumin (PV) demonstrated that the majority of PNN-surrounding cortical neurons are immunoreactive to PV. Similar expression profile of another PNN component tenascin-R was observed in the development of V1. Dark rearing of mice from birth significantly reduced the density of PNN-surrounding neurons. In addition, the expression of two recently identified CSPG receptors — Nogo receptor (NgR) and leukocyte common antigen-related phosphatase (LAR), showed significant increases from PD14 to PD70 in layer 2–6 of cortical PV-positive interneurons in normal reared mice, but decreased significantly in dark-reared ones. Taken together, these results suggest that PNNs form preferentially in cortical PV-positive interneurons in an experience-dependent manner, and reach full maturation around the end of the critical period of V1 development.

Developmental Changes in Postural Stability During the Performance of a Precision Manual Task

Posture becomes integrated with other goal-directed behaviors early in infancy and continues to develop into the second decade of life. However, the developmental time course over which posture is stabilized relative to the base of support during a dynamic manual precision task has not been examined. Postural-manual integration was assessed in 7-year-olds, 10-year-olds, and adults using a postural-manual task in which task precision (target fitting size) and postural difficulty (reaching distance to a target) were manipulated. The main dependent variable was postural time-to-contact (TtC). Results indicated systematic age effects in which TtC was shortest in the 7-year-olds, increased in the 10-year-olds, and was longest in the adults. Across all age levels, TtC was longer when performing a precision ft compared with a nonprecision ft and when fitting at a near target compared with fitting at a far target. Finally, TtC increased over the course of the manual fitting task, suggesting that posture became increasingly stable as the hand approached the opening. The ability to modulate postural TtC during the course of the fitting trial was most pronounced in adults as compared with both groups of children. These results suggest that even by 10-years of age, children are not yet able to fully integrate postural movements with goal directed manual tasks at adult-like levels.

Protection of Neuronal Diversity at the Expense of Neuronal Numbers during Nutrient Restriction in the Drosophila Visual System

SummarySystemic signals provided by nutrients and hormones are known to coordinate the growth and proliferation of different organs during development. However, within the brain, it is unclear how these signals influence neural progenitor divisions and neuronal diversity. Here, in the Drosophila visual system, we identify two developmental phases with different sensitivities to dietary nutrients. During early larval stages, nutrients regulate the size of the neural progenitor pool via insulin/PI3K/TOR-dependent symmetric neuroepithelial divisions. During late larval stages, neural proliferation becomes insensitive to dietary nutrients, and the steroid hormone ecdysone acts on Delta/Notch signaling to promote the switch from symmetric mitoses to asymmetric neurogenic divisions. This mechanism accounts for why sustained undernourishment during visual system development restricts neuronal numbers while protecting neuronal diversity. These studies reveal an adaptive mechanism that helps to retain a functional visual system over a range of different brain sizes in the face of suboptimal nutrition.

DNA Methylation at a Bovine Alpha Satellite I Repeat CpG Site during Development following Fertilization and Somatic Cell Nuclear Transfer

Incomplete epigenetic reprogramming is postulated to contribute to the low developmental success following somatic cell nuclear transfer (SCNT). Here, we describe the epigenetic reprogramming of DNA methylation at an alpha satellite I CpG site (αsatI-5) during development of cattle generated either by artificial insemination (AI) or in vitro fertilization (IVF) and SCNT. Quantitative methylation analysis identified that SCNT donor cells were highly methylated at αsatI-5 and resulting SCNT blastocysts showed significantly more methylation than IVF blastocysts. At implantation, no difference in methylation was observed between SCNT and AI in trophoblast tissue at αsatI-5, however, SCNT embryos were significantly hyper-methylated compared to AI controls at this time point. Following implantation, DNA methylation at αsatI-5 decreased in AI but not SCNT placental tissues. In contrast to placenta, the proportion of methylation at αsatI-5 remained high in adrenal, kidney and muscle tissues during development. Differences in the average proportion of methylation were smaller in somatic tissues than placental tissues but, on average, SCNT somatic tissues were hyper-methylated at αsatI-5. Although sperm from all bulls was less methylated than somatic tissues at αsatI-5, on average this site remained hyper-methylated in sperm from cloned bulls compared with control bulls. This developmental time course confirms that epigenetic reprogramming does occur, at least to some extent, following SCNT. However, the elevated methylation levels observed in SCNT blastocysts and cellular derivatives implies that there is either insufficient time or abundance of appropriate reprogramming factors in oocytes to ensure complete reprogramming. Incomplete reprogramming at this CpG site may be a contributing factor to low SCNT success rates, but more likely represents the tip of the iceberg in terms of incompletely reprogramming. Until protocols ensure the epigenetic signature of a differentiated somatic cell is reset to a state resembling totipotency, the efficiency of SCNT is likely to remain low.

Sensitive and critical periods in visual sensory deprivation

While the demonstration of crossmodal plasticity is well established in congenital and early blind individuals, great debate still surrounds whether those who acquire blindness later in life can also benefit from such compensatory changes. No proper consensus has been reached despite the fact that a proper understanding of the developmental time course of these changes, and whether their occurrence is limited to—or within—specific time windows, is crucial to our understanding of the crossmodal phenomena. An extensive review of the literature reveals that while the majority of investigations to date have examined the crossmodal plasticity available to late blind individuals in quantitative terms, recent findings rather suggest that this reorganization also likely changes qualitatively compared to what is observed in early blindness. This obviously could have significant repercussions not only for the training and rehabilitation of blind individuals, but for the development of appropriate neuroprostheses designed to aid and potentially restore vision. Important parallels will also be drawn with the current state of research on deafness, which is particularly relevant given in the development of successful neuroprostheses (e.g., cochlear implants) for providing auditory input to the central nervous system otherwise aurally deafferented. Lastly, this paper will address important inconsistencies across the literature concerning the definition of distinct blind groups based on the age of blindness onset, and propose several alternatives to using such a categorization.

Developmental Trajectories of Associative Memory from Childhood to Adulthood: A Behavioral and Neuroimaging Study

Episodic memory refers to the capacity to bind multimodal memories to constitute a unique personal event. Most developmental studies on episodic memory focused on one specific component, i.e., the core factual information. The present study examines the relevance of a novel episodic paradigm to assess its developmental trajectories in a more comprehensive way according to the type of association (item-feature, item-location, and item-sequence associations) with measures of both objective and subjective recollection. We conducted a behavioral study aimed at testing the effects of age in a large sample of 160 children, adolescents, and young adults (6–23 years old). We confronted the behavioral data to the neural correlates in a subgroup of 30 children using voxel-based morphometry. Behavioral data outlined differential developmental trajectories according to the type of association, with a continuous increase of factual associative memory efficiency until 10 years, a linear increase of performance in spatial associative memory that pursues until early adulthood and an abrupt increase in temporal associative memory efficiency between 9 and 10. Regarding recollection, measures showed a more pronounced enhancement from 9 to 10 years. Hence, behavioral data highlight a peculiar period in late childhood (8–10 years old) crucial for the developmental time course of episodic memory. Regarding structural data, we found that the improvement of associative memory efficiency was related to a decrease in gray matter volume in a large cerebral network including the dorsolateral and ventrolateral prefrontal cortex (and superior and anterior temporal regions), and the hippocampus bilaterally. These data suggest that multimodal integration would probably be related to the maturation of temporal regions and modulated by a fronto-parietal network. Besides, our findings emphasize the relevance of the present paradigm to assess episodic memory especially in the clinical setting.

Functional circuits of new neurons in the dentate gyrus

The hippocampus is crucial for memory formation. New neurons are added throughout life to the hippocampal dentate gyrus (DG), a brain area considered important for differential storage of similar experiences and contexts. To better understand the functional contribution of adult neurogenesis to pattern separation processes, we recently used a novel synapse specific trans-neuronal tracing approach to identify the (sub) cortical inputs to new dentate granule cells (GCs). It was observed that newly born neurons receive sequential innervation from structures important for memory function. Initially, septal-hippocampal cells provide input to new neurons, including transient innervation from mature GCs as well as direct feedback from area CA3 pyramidal neurons. After about 1 month perirhinal (PRH) and lateral entorhinal cortex (LEC), brain areas deemed relevant to integration of novel sensory and environmental information, become substantial input to new GCs. Here, we review the developmental time-course and proposed functional relevance of new neurons, within the context of their unique neural circuitry.

Benefits of regular aerobic exercise for executive functioning in healthy populations

Research suggests that regular aerobic exercise has the potential to improve executive functioning, even in healthy populations. The purpose of this review is to elucidate which components of executive functioning benefit from such exercise in healthy populations. In light of the developmental time course of executive functions, we consider separately children, young adults, and older adults. Data to date from studies of aging provide strong evidence of exercise-linked benefits related to task switching, selective attention, inhibition of prepotent responses, and working memory capacity; furthermore, cross-sectional fitness data suggest that working memory updating could potentially benefit as well. In young adults, working memory updating is the main executive function shown to benefit from regular exercise, but cross-sectional data further suggest that task-switching and post error performance may also benefit. In children, working memory capacity has been shown to benefit, and cross-sectional data suggest potential benefits for selective attention and inhibitory control. Although more research investigating exercise-related benefits for specific components of executive functioning is clearly needed in young adults and children, when considered across the age groups, ample evidence indicates that regular engagement in aerobic exercise can provide a simple means for healthy people to optimize a range of executive functions.

Parallel maturation of goal-directed behavior and dopaminergic systems during adolescence.

Adolescence is a crucial developmental period characterized by specific behaviors reflecting the immaturity of decision-making abilities. However, the maturation of precise cognitive processes and their neurobiological correlates at this period remain poorly understood. Here, we investigate whether a differential developmental time course of dopamine (DA) pathways during late adolescence could explain the emergence of particular executive and motivational components of goal-directed behavior. First, using a contingency degradation protocol, we demonstrate that adolescent rats display a specific deficit when the causal relationship between their actions and their consequences is changed. When the rats become adults, this deficit disappears. In contrast, actions of adolescents remain sensitive to outcome devaluation or to the influence of a pavlovian-conditioned stimulus. This aspect of cognitive maturation parallels a delayed development of the DA system, especially the mesocortical pathway involved in action adaptation to rule changes. Unlike in striatal and nucleus accumbens regions, DA fibers and DA tissue content continue to increase in the medial prefrontal cortex from juvenile to adult age. Moreover, a sustained overexpression of DA receptors is observed in the prefrontal region until the end of adolescence. These findings highlight the relationship between the emergence of specific cognitive processes, in particular the adaptation to changes in action consequences, and the delayed maturation of the mesocortical DA pathway. Similar developmental processes in humans could contribute to the adolescent vulnerability to the emergence of several psychiatric disorders characterized by decision-making deficits.

An Always Correlated gene expression landscape for ovine skeletal muscle, lessons learnt from comparison with an “equivalent” bovine landscape

BackgroundWe have recently described a method for the construction of an informative gene expression correlation landscape for a single tissue, longissimus muscle (LM) of cattle, using a small number (less than a hundred) of diverse samples. Does this approach facilitate interspecies comparison of networks?FindingsUsing gene expression datasets from LM samples from a single postnatal time point for high and low muscling sheep, and from a developmental time course (prenatal to postnatal) for normal sheep and sheep exhibiting the Callipyge muscling phenotype gene expression correlations were calculated across subsets of the data comparable to the bovine analysis. An “Always Correlated” gene expression landscape was constructed by integrating the correlations from the subsets of data and was compared to the equivalent landscape for bovine LM muscle. Whilst at the high level apparently equivalent modules were identified in the two species, at the detailed level overlap between genes in the equivalent modules was limited and generally not significant. Indeed, only 395 genes and 18 edges were in common between the two landscapes.ConclusionsSince it is unlikely that the equivalent muscles of two closely related species are as different as this analysis suggests, within tissue gene expression correlations appear to be very sensitive to the samples chosen for their construction, compounded by the different platforms used. Thus users need to be very cautious in interpretation of the differences. In future experiments, attention will be required to ensure equivalent experimental designs and use cross-species gene expression platform to enable the identification of true differences between different species.

Behavioral and ERP evidence of word and pseudoword superiority effects in 7- and 11-year-olds

In groups of 7-year-olds and 11-year-olds, event-related potentials (ERPs) were recorded to briefly presented, masked letter strings that included real word (DARK/PARK), pronounceable pseudoword (DARL/PARL), unpronounceable nonword (RDKA/RPKA), and letter-in-xs (DXXX, PXXX) stimuli in a variant of the Reicher-Wheeler paradigm. Behaviorally, participants decided which of two letters occurred at a given position in each string (here, forced-choice alternatives D and P). Both groups showed evidence of behavioral word (more accurate choices for letters in words than in baseline nonwords or letter-in-xs) and pseudoword (more accurate choices for letters in pseudowords than in baseline nonwords or letter-in-xs) superiority effects. Electrophysiologically, 11-year-olds evidenced superiority effects on P150 and N400 peak amplitude, while 7-year-olds showed effects only on N400 amplitude. These findings suggest that the mechanisms underlying the observed behavioral superiority effects may be lexical in younger children but both sublexical and lexical in older children. These results are consistent with a lengthy developmental time course for automatic sublexical orthographic specialization, extending beyond the age of 11.

Evaluation of Normal Human Foveal Development Using Optical Coherence Tomography and Histologic Examination

To assess outer retinal layer maturation during late gestation and early postnatal life using optical coherence tomography and histologic examination. Thirty-nine participants 30 weeks' postmenstrual age or older were imaged using a handheld optical coherence tomography system, for a total of 102 imaging sessions. Foveal images from 16 participants (21 imaging sessions) were normal and evaluated for inner retinal excavation and the presence of outer retinal reflective bands. Reflectivity profiles of central, parafoveal, and parafoveal retina were extracted and were compared with age-matched histologic sections. The foveal pit morphologic structure in infants was generally distinguishable from that in adults. Reflectivity profiles showed a single hyperreflective band at the fovea in all the infants younger than 42 weeks' postmenstrual age. Multiple bands were distinguishable in the outer retina at the peri fovea by 32 weeks' postmenstrual age and at the fovea by 3 months' postterm. By 17 months' postnatal, the characteristic appearance of 4 hyperreflective bands was evident across the foveal region. These features are consistent with previous results from histologic examinations. A "temporal divot" was present in some infants, and the foveal pit morphologic structure and the extent of inner retinal excavation were variable. Handheld optical coherence tomography is a viable technique for evaluating neonatal retinas. In premature infants who do not develop retinopathy of prematurity, the foveal region seems to follow a developmental time course similar to that associated with in utero maturation. As pediatric optical coherence tomography becomes more common, a better understanding of normal foveal and macular development is needed. Longitudinal imaging offers the opportunity to track postnatal foveal development among preterm infants in whom poor visual outcomes are anticipated or to follow up treatment outcomes in this population.

Zinc histochemistry reveals circuit refinement and distinguishes visual areas in the developing ferret cerebral cortex

A critical question in brain development is whether different brain circuits mature concurrently or with different timescales. To characterize the anatomical and functional development of different visual cortical areas, one must be able to distinguish these areas. Here, we show that zinc histochemistry, which reveals a subset of glutamatergic processes, can be used to reliably distinguish visual areas in juvenile and adult ferret cerebral cortex, and that the postnatal decline in levels of synaptic zinc follows a broadly similar developmental trajectory in multiple areas of ferret visual cortex. Zinc staining in all areas examined (17, 18, 19, 21, and Suprasylvian) is greater in the 5-week-old than in the adult. Furthermore, there is less laminar variation in zinc staining in the 5-week-old visual cortex than in the adult. Despite differences in staining intensity, areal boundaries can be discerned in the juvenile as in the adult. By 6weeks of age, we observe a significant decline in visual cortical synaptic zinc; this decline was most pronounced in layer IV of areas 17 and 18, with much less change in higher-order extrastriate areas during the important period in visual cortical development following eye opening. By 10weeks of age, the laminar pattern of zinc staining in all visual areas is essentially adultlike. The decline in synaptic zinc in the supra- and infragranular layers in all areas proceeds at the same rate, though the decline in layer IV does not. These results suggest that the timecourse of synaptic zinc decline is lamina specific, and further confirm and extend the notion that at least some aspects of cortical maturation follow a similar developmental timecourse in multiple areas. The postnatal decline in synaptic zinc we observe during the second postnatal month begins after eye opening, consistent with evidence that synaptic zinc is regulated by sensory experience.

Combinatorial control of temporal gene expression in the Drosophila wing by enhancers and core promoters

BackgroundThe transformation of a developing epithelium into an adult structure is a complex process, which often involves coordinated changes in cell proliferation, metabolism, adhesion, and shape. To identify genetic mechanisms that control epithelial differentiation, we analyzed the temporal patterns of gene expression during metamorphosis of the Drosophila wing.ResultsWe found that a striking number of genes, approximately 50% of the Drosophila transcriptome, exhibited changes in expression during a time course of wing development. While cis-acting enhancer sequences clearly correlated with these changes, a stronger correlation was discovered between core-promoter types and the dynamic patterns of gene expression within this differentiating tissue. In support of the hypothesis that core-promoter type influences the dynamics of expression, expression levels of several TATA-box binding protein associated factors (TAFs) and other core promoter-associated components changed during this developmental time course, and a testes-specific TAF (tTAF) played a critical role in timing cellular differentiation within the wing.ConclusionsOur results suggest that the combinatorial control of gene expression via cis-acting enhancer sequences and core-promoter types, determine the complex changes in gene expression that drive morphogenesis and terminal differentiation of the Drosophila wing epithelium.

High-fidelity promoter profiling reveals widespread alternative promoter usage and transposon-driven developmental gene expression

Many eukaryotic genes possess multiple alternative promoters with distinct expression specificities. Therefore, comprehensively annotating promoters and deciphering their individual regulatory dynamics is critical for gene expression profiling applications and for our understanding of regulatory complexity. We introduce RAMPAGE, a novel promoter activity profiling approach that combines extremely specific 5′-complete cDNA sequencing with an integrated data analysis workflow, to address the limitations of current techniques. RAMPAGE features a streamlined protocol for fast and easy generation of highly multiplexed sequencing libraries, offers very high transcription start site specificity, generates accurate and reproducible promoter expression measurements, and yields extensive transcript connectivity information through paired-end cDNA sequencing. We used RAMPAGE in a genome-wide study of promoter activity throughout 36 stages of the life cycle of Drosophila melanogaster, and describe here a comprehensive data set that represents the first available developmental time-course of promoter usage. We found that >40% of developmentally expressed genes have at least two promoters and that alternative promoters generally implement distinct regulatory programs. Transposable elements, long proposed to play a central role in the evolution of their host genomes through their ability to regulate gene expression, contribute at least 1300 promoters shaping the developmental transcriptome of D. melanogaster. Hundreds of these promoters drive the expression of annotated genes, and transposons often impart their own expression specificity upon the genes they regulate. These observations provide support for the theory that transposons may drive regulatory innovation through the distribution of stereotyped cis-regulatory modules throughout their host genomes.

Critical Period of Experience-Driven Axon Retraction in the Pharmacologically Inhibited Visual Cortex

Monocular deprivation (MD) during the critical period reduces the visual cortical response to the deprived eye and causes the geniculocortical axons serving the deprived eye to retract. When MD is combined with a pharmacological inhibition of the visual cortex, the cortical neurons weaken their response to an open eye and the input axons serving the open eye retract. To determine whether the 2 types of ocular dominance (OD) plasticity reflect an experience-driven modification of neural circuits sharing the same developmental time course, we analyzed the OD plasticity in an inhibited visual cortex using cats at different ages. MD did not affect the OD distribution in the inhibited cortex of adults, confirming that the OD plasticity in the inhibited cortex represents a developmental plasticity. In developing animals, the OD plasticity in the inhibited cortex was observed at the late phase of the critical period (P40-46) but not at the early phase (P22-26). We found a retraction of input axons serving an open eye at the late phase, whereas those at the early phase were comparable to the axons of normal animals. Therefore, the maturation of visual circuits might include an experience-driven rearrangement of thalamocortical projections during the late phase of development.

Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping

The elaboration of the myelinated white matter is essential for normal neurodevelopment, establishing and mediating rapid communication pathways throughout the brain. These pathways facilitate the synchronized communication required for higher order behavioral and cognitive functioning. Altered neural messaging (or ‘disconnectivity’) arising from abnormal white matter and myelin development may underlie a number of neurodevelopmental psychiatric disorders. Despite the vital role myelin plays, few imaging studies have specifically examined its maturation throughout early infancy and childhood. Thus, direct investigations of the relationship(s) between evolving behavioral and cognitive functions and the myelination of the supporting neural systems have been sparse. Further, without knowledge of the ‘normative’ developmental time-course, identification of early abnormalities associated with developmental disorders remains challenging. In this work, we examined the use of longitudinal (T1) and transverse (T2) relaxation time mapping, and myelin water fraction (MWF) imaging to investigate white matter and myelin development in 153 healthy male and female children, 3 months through 60 months in age. Optimized age-specific acquisition protocols were developed using the DESPOT and mcDESPOT imaging techniques; and mean T1, T2 and MWF trajectories were determined for frontal, temporal, occipital, parietal and cerebellar white matter, and genu, body and splenium of the corpus callosum. MWF results provided a spatio-temporal pattern in-line with prior histological studies of myelination. Comparison of T1, T2 and MWF measurements demonstrates dissimilar sensitivity to tissue changes associated with neurodevelopment, with each providing differential but complementary information.

Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea

Correct patterning of the inner ear sensory epithelium is essential for the conversion of sound waves into auditory stimuli. Although much is known about the impact of the developing cytoskeleton on cellular growth and cell shape, considerably less is known about the role of cytoskeletal structures on cell surface mechanical properties. In this study, atomic force microscopy (AFM) was combined with fluorescence imaging to show that developing inner ear hair cells and supporting cells have different cell surface mechanical properties with different developmental time courses. We also explored the cytoskeletal organization of developing sensory and non-sensory cells, and used pharmacological modulation of cytoskeletal elements to show that the developmental increase of hair cell stiffness is a direct result of actin filaments, whereas the development of supporting cell surface mechanical properties depends on the extent of microtubule acetylation. Finally, this study found that the fibroblast growth factor signaling pathway is necessary for the developmental time course of cell surface mechanical properties, in part owing to the effects on microtubule structure.

Humans Mimicking Animals: A Cortical Hierarchy for Human Vocal Communication Sounds

Numerous species possess cortical regions that are most sensitive to vocalizations produced by their own kind (conspecifics). In humans, the superior temporal sulci (STSs) putatively represent homologous voice-sensitive areas of cortex. However, superior temporal sulcus (STS) regions have recently been reported to represent auditory experience or "expertise" in general rather than showing exclusive sensitivity to human vocalizations per se. Using functional magnetic resonance imaging and a unique non-stereotypical category of complex human non-verbal vocalizations-human-mimicked versions of animal vocalizations-we found a cortical hierarchy in humans optimized for processing meaningful conspecific utterances. This left-lateralized hierarchy originated near primary auditory cortices and progressed into traditional speech-sensitive areas. Our results suggest that the cortical regions supporting vocalization perception are initially organized by sensitivity to the human vocal tract in stages before the STS. Additionally, these findings have implications for the developmental time course of conspecific vocalization processing in humans as well as its evolutionary origins.

Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea

Correct patterning of the inner ear sensory epithelium is essential for the conversion of sound waves into auditory stimuli. Although much is known about the impact of the developing cytoskeleton on cellular growth and cell shape, considerably less is known about the role of cytoskeletal structures on cell surface mechanical properties. In this study, atomic force microscopy (AFM) was combined with fluorescence imaging to show that developing inner ear hair cells and supporting cells have different cell surface mechanical properties with different developmental time courses. We also explored the cytoskeletal organization of developing sensory and non-sensory cells, and used pharmacological modulation of cytoskeletal elements to show that the developmental increase of hair cell stiffness is a direct result of actin filaments, whereas the development of supporting cell surface mechanical properties depends on the extent of microtubule acetylation. Finally, this study found that the fibroblast growth factor signaling pathway is necessary for the developmental time course of cell surface mechanical properties, in part owing to the effects on microtubule structure.