Course Of Postnatal Development Research Articles

Early life interventions metformin and trodusquemine metabolically reprogram the developing mouse liver through transcriptomic alterations.

Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds on young, developing mice to uncover biomolecular signatures that are central to liver metabolic processes. We found that MSI-1436 more potently alters mRNA and miRNA expression in the liver compared with MF, with bioinformatic analysis suggesting that cohorts of differentially expressed miRNAs inhibit the action of phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt), and mammalian target of rapamycin (Mtor) to regulate the downstream processes of de novo lipogenesis, fatty acid oxidation, very-low-density lipoprotein transport, and cholesterol biosynthesis and efflux. In summary, our study demonstrates that administering these compounds during the postnatal window metabolically reprograms the liver through induction of potent epigenetic changes in the transcriptome, potentially forestalling the onset of age-related diseases and enhancing longevity. Future studies are necessary to determine the impacts on lifespan and overall quality of life.

Vascular Underpinnings of Cerebral Lateralisation in the Neonate

Traditionally, adult and neonatal cerebral perfusion have been presumed to be symmetrical. Contrary to this, our adult work shows that supra-aortic cerebral supply is systematically biased towards the left, in terms of both vessel geometry and blood flow volumes. Although this asymmetry is meaningfully related to hand preference, the developmental origins of this association remain unknown. Our detailed investigations of the cerebral vasculature confirm analogous asymmetries in term neonates. Specifically, we demonstrate that the structure and flow of neonatal middle cerebral vessels are consistently asymmetric and predominantly left-dominant. Building on our work from the same cohort, we now report further analyses of these new-found asymmetries. Namely, exploring for the first time, the relationship between arterial lateral biases and the neonatal head-turning response—a reliable early behavioural precursor of handedness that shows a systematic rightward bias in the population. Here, we demonstrate a contralateral relationship between vessel morphology and primitive expressions of lateralisation that predate the establishment of definitive handedness in the course of postnatal development. This relationship mimics patterns observed in adults and suggests that lateralising trends in angiogenesis may ultimately influence the emergence of human lateral preferences.

Postnatal development of mouse spermatogonial stem cells as determined by immunophenotype, regenerative capacity, and long-term culture-initiating ability: a model for practical applications

Spermatogonial stem cells (SSCs) are the foundation of life-long spermatogenesis. While SSC research has advanced greatly over the past two decades, characterization of SSCs during postnatal development has not been well documented. Using the mouse as a model, in this study, we defined the immunophenotypic profiles of testis cells during the course of postnatal development using multi-parameter flow cytometry with up to five cell-surface antigens. We found that the profiles progress over time in a manner specific to developmental stages. We then isolated multiple cell fractions at different developmental stages using fluorescent-activated cell sorting (FACS) and identified specific cell populations with prominent capacities to regenerate spermatogenesis upon transplantation and to initiate long-term SSC culture. The data indicated that the cell fraction with the highest level of regeneration capacity exhibited the most prominent potential to initiate SSC culture, regardless of age. Interestingly, refinement of cell fractionation using GFRA1 and KIT did not lead to further enrichment of regenerative and culture-initiating stem cells, suggesting that when a high degree of SSC enrichment is achieved, standard markers of SSC self-renewal or commitment may lose their effectiveness to distinguish cells at the stem cell state from committed progenitors. This study provides a significant information resource for future studies and practical applications of mammalian SSCs.

Intrinsic burst-firing in lamina I spinoparabrachial neurons during adolescence

A subset of glutamatergic interneurons in the neonatal spinal superficial dorsal horn (SDH) exhibits intrinsic burst-firing (i.e. ‘pacemaker’ activity), which is tightly regulated by persistent, voltage-gated Na+ channels and classic inward-rectifying K+ (Kir2) channels and downregulated over the course of postnatal development. Ascending lamina I projection neurons targeting the parabrachial nucleus (PB) or periaqueductal gray (PAG) can also display pacemaker activity during early life. However, the degree to which the ionic mechanisms driving pacemaker activity are conserved across different cell types in the spinal dorsal horn, as well as whether the intrinsic bursting is restricted to newborn projection neurons, remains to be elucidated. Using in vitro patch clamp recordings from identified lamina I spinoparabrachial neurons in rat spinal cord slices, here we demonstrate that adolescent projection neurons retain their ability to generate pacemaker activity. In contrast to previous findings in lamina I interneurons, pacemaker projection neurons possessed higher membrane capacitance, lower membrane resistance, and a greater Kir-mediated conductance compared to adjacent spinoparabrachial neurons that lacked intrinsic burst-firing. Nonetheless, as previously seen in interneurons, the bath application of riluzole to block persistent Na+ channels significantly dampened pacemaker activity in projection neurons. Collectively, these results suggest that intrinsic burst-firing in the developing dorsal horn can be generated by multiple combinations of ionic conductances, and highlight the need for further investigation into the mechanisms governing pacemaker activity within the major output neurons of the SDH network.

Postnatal development of subfields in the core region of the mouse auditory cortex

The core region of the rodent auditory cortex has two subfields: the primary auditory area (A1) and the anterior auditory field (AAF). Although the postnatal development of A1 has been studied in several mammalian species, few studies have been conducted on the postnatal development of AAF. Using a voltage-sensitive-dye-based imaging method, we examined and compared the postnatal development of AAF and A1 in mice from postnatal day 11 (P11) to P40. We focused on the postnatal development of tonotopy, the relative position between A1 and AAF, and the properties of tone-evoked responses in the subfields. Tone-evoked responses in the mouse auditory cortex were first observed at P12, and tonotopy was found in both A1 and AAF at this age. Quantification of tonotopy using the cortical magnification factor (CMF; octave difference per unit cortical distance) revealed a rapid change from P12 to P14 in both A1 and AAF, and a stable level from P14. A similar time course of postnatal development was found for the distance between the 4 kHz site in A1 and AAF, the distance between the 16 kHz site in A1 and AAF, and the angle between the frequency axis of A1 and AAF. The maximum amplitude and rise time of tone-evoked signals in both A1 and AAF showed no significant change from P12 to P40, but the latency of the responses to both the 4 kHz and 16 kHz tones decreased during this period, with a more rapid decrease in the latency to 16 kHz tones in both subfields. The duration of responses evoked by 4 kHz tones in both A1 and AAF showed no significant postnatal change, but the duration of responses to 16 kHz tones decreased exponentially in both subfields. The cortical area activated by 4 kHz tones in AAF was always larger than that in A1 at all ages (P12-P40). Our results demonstrated that A1 and AAF developed in parallel postnatally, showing a rapid maturation of tonotopy, slow maturation of response latency and response duration, and a dorsal-to-ventral order (high-frequency site to low-frequency site) of functional maturation.

Coordinated development of the mitochondrial reticulum in skeletal muscle

Skeletal muscle cells form a mitochondrial network, or reticulum, in a fiber‐type specific manner with grid‐like and fiber‐perpendicular mitochondrial network configurations found in oxidative and glycolytic fibers, respectively. However, it is not well characterized how the networks form during postnatal muscle development. Using focused ion beam scanning electron microscopy (FIB‐SEM) and machine learning based 3D image segmentation and analysis, we have sought to understand the 3D mitochondrial development in oxidative (soleus) and glycolytic (gastrocnemius) muscles of mice at different postnatal days 1 (P1), 14 (P14), and 42 (P42). Both oxidative and glycolytic fibers show tortuous, parallel mitochondrial formations at P1. At P14, oxidative fibers have more elongated, fiber‐parallel mitochondria, while glycolytic fibers have a more grid‐like mitochondrial reticulum. To better understand the intra‐ and inter‐organelle interactions of the mitochondrial reticulum during development, we additionally assessed intermitochondrial junctions (IMJ) and mitochondrial interactions with lipid droplets (LD). During early maturation (P1‐P14), many IMJ in oxidative fibers are arranged in both diagonal (~40%) and parallel (~40%) directions, yet matured oxidative fibers have almost half (~50%) of IMJ in the perpendicular direction. In contrast, after having ~50% of IMJ along the parallel axis at P1, glycolytic fibers gradually change IMJ orientations more into both perpendicular and diagonal axis and IMJ are located in all directions at P42. Although mitochondria in glycolytic fibers maintain similar sizes of the IMJ contact sites between P1 and P14 and have smaller areas at P42, oxidative fibers have ~2‐fold larger IMJ areas at P14 as compared to early (P1) and matured (P42) fibers. Meanwhile, both oxidative and glycolytic fibers at P1 have many, big LD that sharply decrease in size during the course of postnatal development. In the matured muscles, oxidative fibers have few, tiny LD and glycolytic fibers have no LD. Both fibers maintain similar LD contract areas per mitochondrion across P1‐P42. Notably, mitochondria directly in contact with LD have volumes ~2–3‐fold larger than non‐LD‐contacted mitochondria at all time points. In addition, the LD‐contacted mitochondria have ~2‐fold bigger IMJ areas as compared to non‐contacted one, with the largest differences observed at P14. In conclusion, development of the muscle mitochondrial reticulum occurs in coordination with altered interactions among mitochondria and with LD. However, future studies are warranted to study possible interactive roles of calcium handling structures such as sarcoplasmic reticulum and t‐tubules.Support or Funding InformationThis study is supported by intramural programs within the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 1ZIAHL006221‐02).

Biochemical Changes Indicate Developmental Stage in the Hippocampal Formation.

The literature showing how age of humans or animals influences the IR absorption spectra recorded in different brain regions is very poor. A very limited number of studies used FTIR microspectroscopy for analysis of the aging process, however there is lack of data concerning the biomolecular changes occurring in the course of postnatal development of the central nervous system. Therefore, in this paper the topographic and semiquantitative biochemical changes occurring within the rat hippocampus during postnatal development were examined. To achieve the goal of the study, three groups of normal male rats differing in age were investigated. These were 6, 30, and 60 day old animals, and the chosen ages correspond to the neonatal period, childhood, and early adulthood in humans, respectively. Already, preliminary topographic analysis identified a number of significant changes in the accumulation of biomolecules within the hippocampal formation occurring during brain development. Such observation was confirmed by further semiquantitative analysis of intensities of selected absorption bands or ratios of their intensities. The detailed examinations were done for four hippocampal cellular layers (multiform, molecular, pyramidal, and granular layers), and the results showed that the accumulation of most biomolecules, including both saturated and unsaturated lipids as well as compounds containing phosphate and carbonyl groups, was significantly higher in adulthood comparing to the neonatal period. What is more, the increases in their levels were observed mostly between 6th and 30th days of animals' life. The unsaturation level of lipids did not change during postnatal development, although the differences in unsaturated and saturated lipids contents were noticed between examined animal groups. Significant differences in relative secondary structure of proteins were found between young adult rats and animals in neonatal period for which the relative level of proteins with β-type secondary structure was the highest.

Mouse MRI shows brain areas relatively larger in males emerge before those larger in females

Sex differences exist in behaviors, disease and neuropsychiatric disorders. Sexual dimorphisms however, have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. Here, we use manganese-enhanced MRI (MEMRI) to longitudinally image male and female C57BL/6J mice across 9 time points, beginning at postnatal day 3. We recapitulate findings on canonically dimorphic areas, demonstrating MEMRI’s ability to study neuroanatomical sex differences. We discover, upon whole-brain volume correction, that neuroanatomical regions larger in males develop earlier than those larger in females. Groups of areas with shared sexually dimorphic developmental trajectories reflect behavioral and functional networks, and expression of genes involved with sex processes. Also, post-pubertal neuroanatomy is highly individualized, and individualization occurs earlier in males. Our results demonstrate the ability of MEMRI to reveal comprehensive developmental differences between male and female brains, which will improve our understanding of sex-specific predispositions to various neuropsychiatric disorders.

Apoptosis pattern and alterations of expression of apoptosis-related factors of supporting cells in Kölliker's organ in vivo in early stage after birth in rats.

Kolliker’s organ is a temporary but indispensable structure in the development of the cochlea. Supporting cells (SCs) within it release adenosine 5’-triphosphate (ATP), which may play a crucial role in cochlear development before the onset of hearing. To reveal the apoptosis of Kolliker’s organ in new-born rats, we studied the morphological changes and expression of apoptosis-related factors during early postnatal development. We found SCs in Kolliker’s organ decreased in number and changed in appearance along the cochlea apex-to-base gradient, and the expression of caspase-3, caspase-8, caspase- 9 and bcl-2 in Kolliker’s organ of the cochlea fluctuated along the course of postnatal development, with an expression peak at postnatal day 3. This study demonstrates a time-dependent degeneration of Kolliker’s organ during postnatal cochlea development, which might be triggered by endogenous factors.

Development of motor coordination during joint action in mid-childhood

The ability to act jointly with others is a hallmark of primate evolution and is fundamental for human development. In recent years, the study of coordination strategies between individuals performing joint actions has received growing attention. However, when, in the course of post-natal development, this cognitive-motor function emerges is still unknown. Here, we studied dyads of peers aged 6–9 years, as well as adult subjects, while they performed a task where the same action, namely, exerting hand force on an isometric joystick to move a visual cursor from a central toward a peripheral target, was performed in a “solo” and in a social “cooperative” context. The results revealed that during joint action planning, an attempt to synchronize one's own action with that of a partner emerges at 7 years of age, together with a reduction in the duration and variability of the reaction times. A critical time is 8 years, when “solo” performance reaches a high level of accuracy. From this age, another coordination strategy, based on the online monitoring of the peer's behavior, seems to be implemented during the execution of joint action. The motor and cognitive development occurring during childhood are discussed as possible mechanisms mediating, respectively, the capability and the propensity to take into account the peer's behavior for implementing a common action plan.

Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses.

Olfactory axons project from nasal epithelium to the primitive telencephalon before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ but arrive via the rostral migratory stream. Synaptic glomeruli and concentric laminar architecture are unlike other cortices. Fetal olfactory maturation of neuronal differentiation, synaptogenesis, and myelination remains incomplete at term and have a protracted course of postnatal development. The olfactory ventricular recess involutes postnatally but dilates in congenital hydrocephalus. Olfactory bulb, tract and epithelium are repositories of progenitor stem cells in fetal and adult life. Diverse malformations of the olfactory bulb can be diagnosed by clinical examination, imaging, and neuropathologically. Cellular markers of neuronal differentiation and synaptogenesis demonstrate immaturity of the olfactory system at birth, previously believed by histology alone to occur early in fetal life. Immaturity does not preclude function.

Analysis of development of morphophunctional interconnections between CART- and AGRPergic neurons with dopaminergic structures in ontogenesis of mammals

There are obtained data indicating that morphogenesis and, probably, formation of structurally functional interaction of the CART- and dopaminergic neurons occur as early as during embryonic development. Meanwhile development of the AGRergic system and formation of its structural and functional communications are observed in the course of postnatal development of rat. Analysis of literature and re- sults of our own investigation show that differentiation of dopaminergic neurons in hypothalamus and midbrain occurs on the background of development of CARTergic neurons and in the absence of AGRP. Taking into account our data on activating action of the CART-peptide and inhibitory effect of AGRP on dopaminergic brain neurons, we believe that the leading component at formation of functional interactions of these systems is the later maturing AGRPergic system.

Morphological diversity in the postnatal skull development in representatives of two families of rodents (Spalacidae, Castoridae, Rodentia)

This is the first study to describe the results of measurement of three information parameters of morphological diversity (entropy, the measure of organization, and the Kullback-Leibler divergence) in the course of postnatal development of the skull in the populations of two rodent species (greater mole rat (Spalax microphthalmus Guld.) and Eurasian beaver (Castor fiber (L.)). The terms "morphosystem" and "morphological space" and its structure are introduced. Within the framework of the developed approach, "morphological diversity" is considered as a variable associated with the morphological space structure. Testing the hypothesis of the dominance of self-organization processes and an increase in the organization of the morphological diversity of the skull in the course ofontogeny showed its inconsistency. The morphosystem of the skull of the studied species undergoes transitions between more organized and less organized states, periodically approaching and departing from the "steady state." Such dynamics characterizes the morphosystem of the skull as a dynamic and nonlinear system.

Plasma Membrane Density of GABAB-R1a, GABAB-R1b, GABA-R2 and Trimeric G-proteins in the Course of Postnatal Development of Rat Brain Cortex

With the aim to understand the onset of expression and developmental profile of plasma membrane (PM) content /density of crucial components of GABA(B)-R signaling cascade, GABA(B)-R1a, GABA(B)-R1b, GABA(B)-R2, G(i)1/G(i)2alpha, G(i)3alpha, G(o)alpha, G(z)alpha and Gbeta subunit proteins were determined by quantitative immunoblotting and compared in PM isolated from brain cortex of rats of different ages: between postnatal-day-1 (PD1) and 90 (PD90). PM density of GABA(B)-R1a, GABA(B)-R2, G(i)1/G(i)2alpha, G(i)3alpha, G(o)alpha, G(z)alpha and Gbeta was high already at birth and further development was reflected in parallel decrease of both GABA(B)-R1a and GABA(B)-R2 subunits. The major decrease of GABA(B)-R1a and GABA(B)-R2 occurred between the birth and PD15: to 55 % (R1a, **) and 51 % (R2, **), respectively. Contrarily, PM level of the cognate G-proteins G(i)1/G(i)2alpha, G(i)3alpha, G(o)alpha, G(z)alpha and Gbeta was unchanged in the course of the whole postnatal period of brain cortex development. Maturation of GABA(B)-R cascade was substantially different from ontogenetic profile of prototypical plasma membrane marker, Na, K-ATPase, which was low at birth and further development was reflected in continuous increase of PM density of this enzyme. Major change occurred between the birth and PD25. In adult rats, membrane content of Na, K-ATPase was 3-times higher than around the birth.

Postsynaptic FMRP bidirectionally regulates excitatory synapses as a function of developmental age and MEF2 activity

Rates of synapse formation and elimination change over the course of postnatal development, but little is known of molecular mechanisms that mediate this developmental switch. Here, we report that the dendritic RNA-binding protein fragile X mental retardation protein (FMRP) bidirectionally and cell autonomously regulates excitatory synaptic function, which depends on developmental age as well as function of the activity-dependent transcription factor myocyte enhancer factor 2 (MEF2). The acute postsynaptic expression of FMRP in CA1 neurons of hippocampal slice cultures (during the first postnatal week, P6-P7) promotes synapse function and maturation. In contrast, the acute expression of FMRP or endogenous FMRP in more mature neurons (during the second postnatal week; P13-P16) suppresses synapse number. The ability of neuronal depolarization to stimulate MEF2 transcriptional activity increases over this same developmental period. Knockout of endogenous MEF2 isoforms causes acute postsynaptic FMRP expression to promote, instead of eliminate, synapses onto 2-week-old neurons. Conversely, the expression of active MEF2 in neonatal neurons results in a precocious FMRP-dependent synapse elimination. Our findings suggest that FMRP and MEF2 function together to fine tune synapse formation and elimination rates in response to neuronal activity levels over the course of postnatal development.

Developmental regulation of expression of schizophrenia susceptibility genes in the primate hippocampal formation

The hippocampal formation is essential for normal memory function and is implicated in many neurodevelopmental, neurodegenerative and neuropsychiatric disorders. In particular, abnormalities in hippocampal structure and function have been identified in schizophrenic subjects. Schizophrenia has a strong polygenic component, but the role of numerous susceptibility genes in normal brain development and function has yet to be investigated. Here we described the expression of schizophrenia susceptibility genes in distinct regions of the monkey hippocampal formation during early postnatal development. We found that, as compared with other genes, schizophrenia susceptibility genes exhibit a differential regulation of expression in the dentate gyrus, CA3 and CA1, over the course of postnatal development. A number of these genes involved in synaptic transmission and dendritic morphology exhibit a developmental decrease of expression in CA3. Abnormal CA3 synaptic organization observed in schizophrenics might be related to some specific symptoms, such as loosening of association. Interestingly, changes in gene expression in CA3 might occur at a time possibly corresponding to the late appearance of the first clinical symptoms. We also found earlier changes in expression of schizophrenia susceptibility genes in CA1, which might be linked to prodromal psychotic symptoms. A number of schizophrenia susceptibility genes including APOE, BDNF, MTHFR and SLC6A4 are involved in other disorders, and thus likely contribute to nonspecific changes in hippocampal structure and function that must be combined with the dysregulation of other genes in order to lead to schizophrenia pathogenesis.

Biological maturity at birth, the course of the subsequent ontogenetic stages and age at menarche

The main aim of the study was to assess the influence of biological maturity at birth on growth processes in the subsequent years and during puberty in girls. The material of this study comes from the outpatient clinic cards and cross-sectional research on girls from the province of Wielkopolska in Poland. It includes data of 527 girls. The influence of perinatal maturity on body weight in the later stages of ontogeny was determined with the use of the Kruskal–Wallis test and the Mann–Whitney U test. In order to determine the relationship between perinatal maturity and age at menarche, the survival analysis module was used.The results show a diverse influence of perinatal maturity on the values of body weight achieved in later years of life. The indicated predictive factors included both birth weight and gestational age. In the examined girls menarche occurred between the 10th year and the 17th year of life (X¯=12.87, s=1.26; Me=13 years). The comparison showed a significant variation in age at menarche depending on the length of pregnancy (log-rank χ22=27.068, p<0.0001) and birth weight (log-rank χ22=23.241, p<0.0001). There was no variation in maturation of the examined girls conditioned by the occurrence of intra-uterine growth retardation (log-rank χ22=2.046, p>0.05). Remote prognoses as to the postnatal development of preterm-born children and/or children with low birth weight indicate adverse influence of these variables on age at menarche. Perinatal biological maturity of a newborn conditions the course of postnatal development.

Recovery of axonal myelination sheath and axonal caliber in the mouse corpus callosum following damage induced by N,N‐diethyldithiocarbamate

Disulfiram is an aldehyde dehydrogenase inhibitor used for the treatment of alcohol dependence and of cocaine addiction. It has been demonstrated that subchronic administration of disulfiram or N,N-diethyldithiocarbamate (DEDTC), the main derivative of disulfiram, to rats can produce central-peripheral distal axonopathy. However, few data regarding the axonal effects of these compounds in the central nervous system exist. Our previous studies have revealed DEDTC-induced axonal damage in the mouse brain during the course of postnatal development, together with alterations in axonal pathfinding and in the myelination process, with partial recovery during the post-treatment period. In order to gather new data about how this axonal damage and recovery occurs in the central nervous system, we performed an ultrastructural analysis of the axons located in the corpus callosum from mice treated with DEDTC during postnatal development. The axonal caliber throughout the axonal area, the maximum axonal diameter, the maximum fiber diameter, and the axonal circularity, at different postnatal stages [from postnatal day (P)9 to P30], were analyzed. In addition, parameters related to the myelinization process (number of myelinated axons, sheath thickness, and the ratio of myelinated axons to total axons) were evaluated. A reduction in the average value of axonal caliber during treatment and a delay in the axonal myelination process were detected. Whereas early recovery of individual axons occurred after treatment (P22), complete recovery of myelinated axons occurred at late postnatal stages (P42). Therefore, chronic treatment with dithiocarbamates requires periods of rest to encourage the recovery of myelinated axons.

Age-related changes in nitroxidergic neurons in some nuclei of rat medulla oblongata

The paper presents a comparative study of NO neurons in the solitary tract nucleus, giant-cell, and lateral reticular nuclei in rats at 4, 7, 10, 14, 30, 45, and 60 days old and 3, 6, 12, 18, 24 months old. We determine the active quantitative and qualitative changes that occur in NO-positive neurons in the studied nuclei during the course of postnatal development. A low level of enzyme activity is observed on the first day; it reaches a peak level around the first-third month, then slowly declines. The size and number of nitroxidergic neurons increases, while the relative cell density decreases until the third month of life. We reveal local differences in the ontogenetic development of NO neurons in the studied nuclei. Solitary tract neurons have the highest rate of development, while NO neurons of old animals undergo early and extreme changes as compared to other studied nuclei of rat medulla oblongata.

Characterization of the transcripts and protein isoforms for cytoplasmic polyadenylation element binding protein-3 (CPEB3) in the mouse retina

BackgroundCytoplasmic polyadenylation element binding proteins (CPEBs) regulate translation by binding to regulatory motifs of defined mRNA targets. This translational mechanism has been shown to play a critical role in oocyte maturation, early development, and memory formation in the hippocampus. Little is known about the presence or functions of CPEBs in the retina. The purpose of the current study is to investigate the alternative splicing isoforms of a particular CPEB, CPEB3, based on current databases, and to characterize the expression of CPEB3 in the retina.ResultsIn this study, we have characterized CPEB3, whose putative role is to regulate the translation of GluR2 mRNA. We identify the presence of multiple alternative splicing isoforms of CPEB3 transcripts and proteins in the current databases. We report the presence of eight alternative splicing patterns of CPEB3, including a novel one, in the mouse retina. All but one of the patterns appear to be ubiquitous in 13 types of tissue examined. The relative abundance of the patterns in the retina is demonstrated. Experimentally, we show that CPEB3 expression is increased in a time-dependent manner during the course of postnatal development, and CPEB3 is localized mostly in the inner retina, including retinal ganglion cells.ConclusionThe level of CPEB3 was up-regulated in the retina during development. The presence of multiple CPEB3 isoforms indicates remarkable complexity in the regulation and function of CPEB3.