Importance Of Developmental Factors Research Articles

Maternal Transmission Effect of a PDGF-C SNP on Nonsyndromic Cleft Lip with or without Palate from a Chinese Population

Cleft lip with or without palate (CL/P) is a common congenital anomaly with a high birth prevalence in China. Based on a previous linkage signal of nonsyndromic CL/P (NSCL/P) on the chromosomal region 4q31–q32 from the Chinese populations, we screened the 4q31–q32 region for susceptibility genes in 214 trios of Han Chinese. PDGF-C, an important developmental factor, resides in the region and has been implicated in NSCL/P. However, in our family-based association test (transmission disequilibrium test; TDT), we could not conclude an association between PDGF-C and NSCL/P as previously suggested. Instead, we found strong evidence for parent-of-origin effect at a PDGF-C SNP, rs17035464, by a likelihood ratio test (unadjusted p-value = 0.0018; Im = 2.46). The location of rs17035464 is 13 kb downstream of a previously reported, NSCL/P-associated SNP, rs28999109. Furthermore, a patient from our sample trios was observed with a maternal segmental uniparental isodisomy (UPD) in a region containing rs17035464. Our findings support the involvement of PDGF-C in the development of oral clefts; moreover, the UPD case report contributes to the collective knowledge of rare variants in the human genome.

The relation between receptive language development and social skills among 4-to-6 year-old Persian-speaking children

Introduction: Language and social skills, the two distinctive characteristics of mankind, play an important role in human life. The acquisition of speech and language, which is regarded to as one of the most important developmental factors, is totally dependent on social interaction. The aim of the current study was to determine the relation between the development of receptive language and selected aspects of social skills in 4-to-6 year-old Persian-speaking children. Materials and Methods: 123 normal Persian-speaking children with the age range of 4 to 6 years (76 boys and 47 girls) who met the inclusionary criteria were recruited from Shiraz kindergartens via a multistage random selection method. The Test of Language Development was first administered to evaluate the subjects’ linguistic skills and the Social Skills Rating System, which includes two teacher and parent questionnaire forms, was then employed to complete the assessment. Data were statistically analyzed via Pearson’s correlation coefficient using SPSS software version 16. Significance level was set at less than or equal to 0.05. Results: The correlation between receptive language and selected dimensions of social skills was significant (P 0.01). Moreover, there was no significant correlation between teachers and parent forms (P > 0.01). Conclusion: These findings showed a positive significant correlation between the development of receptive language and selected aspects of social skills. However, it was only the case for teachers’ form. It is maybe due to the differences in home and educational environment when it comes to teaching children social skills. Considering this difference, crucial training in both environments should be provided for children because of their role in improving the development of receptive language. Keywords: Receptive language, Social skills, Children, Persian-speaking Type of article: Original article

Le Grange D, Lock J (eds): Eating Disorders in Children and Adolescents—A Clinical Handbook

Eating disorders commonly become manifest during late childhood and adolescence. It is thus indeed time for an edited volume that focuses on eating disorders in this age range. Daniel Le Grange and Jim Lock—two distinguished specialists in the treatment of young patients with eating disorders—have undertaken this valuable task. Their book is divided into seven parts, each one of which includes one to eleven articles written by experts in the respective fields. The first part (Aetiology and Neurobiology; Kaye; Racine and co-workers) expands on state and trait markers of anorexia nervosa (AN) and covers the neurobiology of appetite, imaging studies and reward processing in patients with AN. Twin studies have revealed moderate heritability estimates for eating disorders and disordered eating. The finding that variance in disordered eating was predominantly due to shared and non-shared environmental effects in 11-year-old twins in contrast to high heritability estimates in 17-year-old twins underscores the importance of developmental factors. Neurobiological hypotheses to explain the female predominance of eating disorders include the influence of oestrogen and estradiol, the rapid change in body composition during female puberty and the neuropeptides modulating metabolism. Molecular genetic findings are not dealt with; however, it should be pointed out that genome-wide significant loci have not been identified for any eating disorder in contrast to obesity, for which over 30 predisposing single nucleotide polymorphisms have been confirmed. Strobe and Peris in a ‘neuroscience perspective’ of the aetiological role of the family environment analyse the typical life history of patients, which is rarely burdened with conspicuous vulnerability. The importance of gene–environment effects is stressed. Throughout Part 1, the importance of anxiety in the aetiology of eating disorders is looked upon from different perspectives. Part 2—Epidemiology and Course: In spite of a substantial increase in epidemiological studies over the past 30 years, data on children and adolescents remains inconsistent and inadequate. Norris and co-workers summarize incidence and prevalence rates for AN, bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS). Whereas it is uncertain if these rates have increased overall, the adolescent rates have seemingly increased potentially due to an earlier age of onset. Steinhausen reviews the outcome literature including mortality, global outcome, psychiatric disorders at follow-up and prognostic factors for both AN and BN. Part 3—Diagnosis and Classification: Bryant-Waugh and Nicholls and Eddy et al. focus on issues related to diagnosis and classification of disordered eating in childhood and adolescence, respectively. It has been proposed to eliminate the division into child and adolescent versus adult feeding and eating disorders for both ICD-11 and DSM-5. Part 4—Medical Issues and Assessment: Katzman and Findlay provide a synopsis of the medical issues and complications of eating disorders that have been reported in children and adolescents including electrolyte imbalances, renal, cardiovascular, oro-gastrointestinal, endocrine and haematological complications. Loeb et al. address the assessment of eating disorders in children and adolescents. This section of the appropriate way to operationalize low body weight leaves the reader with more questions than answers; it remains unclear as to how a paediatrician or a J. Hebebrand (&) Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany e-mail: Johannes.Hebebrand@uni-due.de

Protective Predictors of Alcohol Use Trajectories Among Canadian Aboriginal Youth

Some Aboriginal youth are at disproportionate risk of using substances and developing abuse and dependence disorders. However, not all Aboriginal youth misuse substances and limited research has examined the protective factors conferring against substance use among these youth. The present study aimed to identify protective factors related to the alcohol use trajectories from early adolescence to emerging adulthood among off-reserve Canadian Aboriginal youth. Participants (N = 330; 50.3% male) aged 12-23 were selected from cycles 2-7 of Statistics Canada's NLSCY. Multilevel modeling was employed to identify protective factors for two constructs of alcohol use. Participation in weekly activities and optimism were found to be protective for both the frequency of alcohol use and heavy drinking trajectories. Attendance of religious services was also found to be protective for heavy drinking behaviors. In contrast, positive peer relationships were a risk factor for frequency of alcohol use, but not heavy drinking. The results provide preliminary evidence of important developmental factors to integrate into substance use intervention programs targeting Aboriginal youth.

Developmental Plasticity and Epigenetic Mechanisms Underpinning Metabolic and Cardiovascular Diseases

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

COMPARATIVE STUDY OF DEVELOPMENTAL EVENTS IN AUTISTIC CHILDREN AND NORMAL CHILDREN

Introduction: Autism is a complicated developmental disability that typically appears during the first three years of life as a result of a neurological disorder affecting performance. The present study aimed at studying significant developmental events happening to autistic children compared to those occurring for normal ones. Materials and Methods: 50 autistic children and 50 normal children with an age range of 4 to 11 years participated in this descriptive-analytic study which was conducted in Isfahan-Iran. Important developmental factors related to pre-, peri- and post-natal periods were collected from literature and a tailor-made questionnaire was designed to be later completed by children's mothers. The data was statistically analyzed via Chi-Square, Fischer Exact and Mann-Whitney test. Results : The results indicated that the factors which occurred significantly more frequently among children with autism were as follows: advanced maternal and paternal age, maternal stress, allergic signs during pregnancy, familial marriages, having a history of communication and/or speech-language disorders in the family, cesarean delivery, high fever after birth, seizures and head trauma (P < 0/05). Conclusion: Although this study cannot determine decisive causes of development of autism in children, it can introduce possible risk factors. In fact, our findings suggest that pre-natal, neonatal and post-natal factors contributing to deviant growth are important in the pathogenesis of the disorder. Keywords: Autism disorder, Normal children, Developmental events, Pre-natal events, Post-natal events

Abstract C150: SOX9 modulates Wnt/beta-catenin singal in cancer cells by regulating TCF4 and LRP6 expression

Abstract Introduction: Cancers frequently exploit developmental genes/pathways to sustain their uncontrolled growth or invasion. SOX9, an important developmental transcription factor is one of the signature genes of the basal-like breast cancers. SOX9 over-expression has been demonstrated in various cancers and is associated with a poor prognosis. In prostate cancer, SOX9 supports tumor proliferation, angiogenesis and local invasion in xenografts. The role of SOX9 as a biomarker and molecular mechanisms of its biological functions were further explored in this study. Methods: Immunohistochmical analysis of SOX9 protein expression was performed on a tissue microarray of 129 breast cancer samples. Gene profiles of the breast cancer samples were examined by ANOVA analysis to identify genes that are expressed at significantly higher level among SOX9-high protein expressing samples. SOX9 regulated genes were validated by their corresponding changes in expression levels to SOX9 silencing in cancer cell lines. The effect of SOX9 silencing on cancer progression was examined in the MCF10A DCIS.com xenografts. Results: SOX9 protein expression was highly represented in the basal-like breast cancers and was associated with poor tumor grades. Among the genes correlated with higher SOX9 expression were two major components of the canonical Wnt/ -catenin signal pathway, ie TCF4 and LRP6. These genes were up- or down-regulated in various cancer cell lines in response to SOX9 overexpression or silencing. More importantly, the Wnt3a induced -catenin activity was significantly reduced when SOX9 protein was specifically down-regulated. SOX9 down-regulation in MCF10A DCIS xenografts lead to a squamous differentiation and a block in the progression from DCIS to invasive carcinoma. Conclusion: This study identified a novel function of SOX9 in modulating Wnt/β-catenin signaling by regulating TCF4 and LRP6 expression. SOX9 enhanced Wnt/β-catenin activity in the absence of APC or β-catenin mutations may play an important role in determining tumor subtype, maintaining tumor stem cells or supporting tumor growth or progression. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C150.

Adolescent Obesity and Puberty: The “Perfect Storm”

Obesity is the most serious long-term health risk currently facing America's adolescents. Weight gain during adolescence carries a higher risk for adult obesity and the metabolic syndrome. This review highlights early adolescence as a particularly high-risk time for weight gain due to the synergy of naturally occurring metabolic changes along with increasing behavioral risk factors. One of the first potential health effects of abnormal weight gain during this period is earlier puberty, usually manifested as thelarche. The obesity epidemic is clearly implicated in the national trend toward earlier thelarche, although the data are not as strong in relation to menarche. Leptin activation of the hypothalamic-pituitary axis, combined with insulin resistance, and increased adiposity may result in the higher estrogen levels that are linked to breast development. Young adolescents also experience a sharp decline in their level of physical activity, worsening nutritional habits, and other important psychosocial and developmental risk factors that may contribute to obesity and estrogen-dependent disease in later life, including polycystic ovary syndrome and breast cancer. Unfortunately, the very psychosocial factors that contribute to abnormal weight gain during early adolescence make prevention and treatment in this population particularly challenging. Therefore, intervening prior to pubertal onset becomes even more important given the risk factors present once puberty begins.

Genes important for early development display promoter hypomethylation in zebrafish sperm

Fertilization involves the joining of sperm and egg to form a pluripotent zygote. One key question for development is whether the promoters of genes important for pluripotency, or for guiding early development (transcription and signaling factors), bear chromatin marks or composition that facilitate their expression at the onset of zygotic transcription. As mature sperm are reported to be transcriptionally inactive and have much higher levels of DNA methylation than somatic cells (or eggs), it has been assumed that the sperm genome is essentially inert, is largely reprogrammed by the egg chromatin, and makes only a few unique contributions to development: the sex chromosome, paternal imprints and certain RNA molecules. To test the status of sperm chromatin, we performed genome‐wide DNA methylation profiling on zebrafish sperm and adult tissues. Surprisingly, although zebrafish sperm is globally hypermethylated, the promoters of many genes encoding important developmental transcription factors and signaling proteins are distinctly hypomethylated. This raises the interesting possibility that certain genes are poised in sperm by hypomethylation to assist in their expression in the developing embryo. Our current efforts to understand how DNA methylation levels are correlated with, and related to, histone modifications will also be presented.

Advances in Postacute Rehabilitation After Childhood-Acquired Brain Injury

Despite traditional views, children do not necessarily recover well from brain injury. Residual functional impairments are commonly documented in physical, cognitive, educational, behavioral, and social domains and result in a significant, ongoing social and economic burden for the child's family and for the broader community. More recent acknowledgment of the serious, and often permanent, consequences of acquired brain injury in childhood has been paralleled by rapid advances in evidence-based, acute medical care and diagnostic technology. In contrast, child-based postacute rehabilitation and long-term interventions are less well developed. To date, child services have borrowed substantially from adult models, combining both direct therapies and interdisciplinary approaches. Despite their proliferation, and strong clinical support, such services are rarely the subject of rigorous evaluation and have given little acknowledgment to the important developmental factors that need to be considered when working with children. Using a developmental framework, this review aims to consider the nature of functional impairments that result from childhood traumatic brain injury, the recovery process postinjury, and the scope and role of child-based rehabilitation. In addition, the relatively scarce body of literature describing the evaluation of child rehabilitation models are reviewed with an emphasis on identifying approaches that provide evidence of enhanced function in the child's everyday life and, in particular, in the home and school contexts.

P21Waf1 inhibits granulocytic differentiation of 32Dcl3 cells

Defining the molecular mechanisms that prevent myeloid progenitor cells from maturing is important because defects in maturation contribute to the development of myeloproliferative and myelodysplastic diseases. IL-3 is an important developmental factor for myeloid progenitor cells in vivo and is required to maintain the undifferentiated state in the 32Dcl3 cell line. The mechanisms employed by IL-3 to block differentiation, however, are not well understood. 32Dcl3 cells are myeloid progenitor cells of murine origin with high basal levels of p21waf1/cip1 (p21) expression. Our laboratory has previously reported that p21 levels decreased as CD34+-derived myeloid progenitor cells underwent terminal granulopoiesis in vitro. The effect of p21 upon the expression of genes associated with granulocytic differentiation has been unexplored, however. Since IL-3 maintains high levels of p21 in 32Dcl3 cells, we tested the hypothesis that p21 is an inhibitor of myeloid differentiation. Our findings demonstrate that siRNA knockdown of murine p21 is correlated with premature expression of the primary granule proteins myeloperoxidase and proteinase-3, proteins not abundant in cells maintained as myeloblasts by IL-3. Rescue with human p21 in these cells suppressed premature granule protein expression. p21 knockdown was also found to accelerate morphologic granulocytic differentiation in 32Dcl3 cells stimulated with G-CSF. Since high expression levels of p21 and overexpression of the IL-3 receptor have been correlated with poor outcomes in acute myeloid leukemias (AML), differentiation blockade by p21 may be one mechanism that contributes to AML pathogenesis.

Neuropeptides and retinal development.

Different peptidergic systems have been investigated with some detail during retinal development, including substance P (SP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) and somatostatin (SRIF). Concerning possible developmental actions of neuropeptides, VIP and PACAP exert protective and growth-promoting actions that may sustain retinal neurons during their development. In addition, the presence of transient SRIF expressing cells and recent observations in SRIF receptor knock out mice indicate variegated roles of this peptide in the development of the retina and of retinofugal projections. Finally, recent studies have shown that, in the developing rabbit retina, changes in the expression pattern of SP receptors are accompanied by modifications of SP physiological effects, indicating that retinal circuits where SP is involved are likely to function in a substantially different manner before the retina becomes involved in the processing of visual stimuli. SP neurotransmission in the immature retina may subserve developmental events, and SP is likely to represent an important developmental factor for the maturation of retinal neurons and circuitries.

Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin.

Lymphoid Enhancer Factor 1 (Lef-1) is an important developmental transcription factor required for the inductive formation of several epithelial-derived organs including hair follicles. Inductive expression of Lef-1 mRNA is tightly regulated during embryo development, suggesting the involvement of a highly regulated promoter. In vitro analysis of the Lef-1 gene has demonstrated the existence of at least two spatially distinct promoters with multiple transcriptional start sites that are responsive to the canonical Wnt/beta-catenin pathway. Regions of the Lef-1 promoter required for inductive regulation in vivo, however, have yet to be determined. To this end, we utilized LacZ-reporter transgenic mice to define segments of the human Lef-1 promoter capable of reproducing mesenchymal- or epithelial-restricted transcriptional patterns of Lef-1 expression during hair and vibrissa follicle development. These studies have revealed that a 110 bp Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1 promoter, plays an important role in regulating mesenchymal, and potentially epithelial, expression during follicle development in mouse embryos. This 2.5 kb Lef-1 promoter also demonstrated inductive mesenchymal expression during postnatal anagen stage hair-follicle cycling. Additionally, analysis of Lef-1 promoter expression revealed previously uncharacterized regions of endogenous Lef-1 expression seen in the sebaceous glands of vibrissa and hair follicles in transgenic lines harboring the minimal Lef-1 promoter and additional intronic sequences. In summary, these studies have begun to dissect the transcriptional diversity of the human Lef-1 promoter during the hair/vibrissa follicle and sebaceous gland formation.

Neurokinin 1 receptor expression and substance p physiological actions are developmentally regulated in the rabbit retina

We investigated the expression of the substance P (SP) receptor (the neurokinin 1 receptor, NK1 receptor) and SP functional effects in developing rabbit retinas. NK1 receptors in adult retinas were in a population of cone bipolar cells and in dopaminergic amacrine cells, as previously described. In contrast, at birth and at postnatal day (PND) 6, NK1 receptors were exclusively expressed by cholinergic amacrine and displaced amacrine cells. NK1 receptor expression in cholinergic cells was still observed at PND10 (eye opening), while at PND21 it was confined to cholinergic cells of the inner nuclear layer. Starting at PND10, NK1 receptors were also in bipolar cells and in dopaminergic amacrine cells. A fully mature NK1 receptor expression pattern was observed at PND35. Dopamine release was assessed in isolated retinas in the presence of SP, the NK1 receptor agonist GR73632 or the NK1 receptor antagonist GR82334. At PND35, extracellular dopamine was significantly increased by 10 μM SP or 0.01–100 μM GR73632, and it was decreased by 0.01–10 μM GR82334. No effects were detected in developing retinas up to PND21. Ca 2+ imaging experiments were performed in single cholinergic cells identified by their “starburst” morphology in perinatal retinas. Intracellular Ca 2+ levels were significantly increased by 1 μM SP or GR73632. This effect was reversibly inhibited by 1 μM GR82334. These data demonstrate that both NK1 receptor expression and SP physiological actions are developmentally regulated in the retina. SP neurotransmission in the immature retina may subserve developmental events, and SP is likely to represent an important developmental factor for the maturation of retinal neurons and circuitries.

A gene expression profile for endochondral bone formation: oligonucleotide microarrays establish novel connections between known genes and BMP-2-induced bone formation in mouse quadriceps

Endochondral bone formation has been fairly well characterized from a morphological perspective and yet this process remains largely undefined at molecular and biochemical levels. In vitro and in vivo studies have shown that human bone morphogenetic protein-2 (hBMP-2) is an important developmental growth and differentiation factor, capable of inducing ectopic bone formation in vivo. This study evaluated several aspects of the osteogenic effect of hBMP-2 protein injected into quadriceps of female C57B1/6J SCID mice. Mice were euthanized 1, 2, 3, 4, 7, and 14 days postinjection and muscles were collected for several methods of analysis. Hematoxylin and eosin-stained sections of muscles injected with formulation buffer showed no evidence of osteogenesis. In contrast, sections of muscles injected with hBMP-2 showed evidence of endochondral bone formation that progressed to mineralized bone by day 14. In addition, radiographs of mice injected with hBMP-2 showed that much of the quadriceps muscle had undergone mineralization by day 14. Labeled mRNA solutions were prepared and hybridized to oligonucleotide arrays designed to monitor ∼1300 murine, full-length genes. Changes in gene expression associated with hBMP-2 were determined from time-matched comparisons between buffer and hBMP-2 samples. A gene expression profile was created for 215 genes that showed greater than 4-fold changes at one or more of the indicated time points. One hundred twenty-two of these genes have previously been associated with bone or cartilage metabolism and showed significant increases in expression, e.g., aggrecan ( Agc1), runt related transcription factor 2 ( Runx2), bone Gla protein 1 ( Bglap1), and procollagens type II ( Col2a1) and X ( Col10a1). In addition, there were 93 genes that have not been explicitly associated with bone or cartilage metabolism. Two of these genes, cytokine receptor-like factor-1 ( Crlf1) and matrix metalloproteinase 23 ( Mmp23), showed peak changes in gene expression of 15- and 40-fold on days 4 and 7, respectively. In situ hybridizations of muscle sections showed that Mmp23 and Crlf1 mRNAs were expressed in chondrocytes and osteoblasts, suggesting a role for both proteins in some aspect of cartilage or bone formation. In conclusion, oligonucleotide arrays enabled a broader view of endochondral bone formation than has been reported to date. An increased understanding of the roles played by these gene products will improve our understanding of skeletogenesis, fracture repair, and pathological conditions such as osteoporosis.

What changes in infant walking and why.

This study compared the relative contributions of growing body dimensions, age, and walking experience in the development of walking skill in 9- to 17-month-old infants (N = 210), 5-6-year old kindergartners (N = 15), and college students (N = 13). Kinematic measures derived from participants' footprints showed characteristic improvements in walking skill. As children became bigger, older, and more experienced, their steps became longer, narrower, straighter, and more consistent. Improvements reflected a narrowing base of support and increasing control over the path of progression. Although both infants' age and the duration of their walking experience contributed to improvements in walking skill, experience was the stronger predictor. This finding suggests that practice is the more important developmental factor for helping infants to conquer their weak muscles and precarious balance.

Conduct Problems, Substance Use and Social Anxiety: A Developmental Study of Recovery and Adaptation

To evaluate the individual developmental significance of disruptive behavior during adolescence, a 16-year-old boy in day treatment for substance abuse was examined. Over the course of 12 weeks, this youth was evaluated in group, individual and family therapy. Before developing conduct disorder symptoms and substance abuse, he was found to have a biological predisposition toward anxiety, and a premorbid history of anxiety and depression. The role of these conduct problems and substance use in alleviating this youth’s isolation and loneliness are considered, as are the maladaptive consequences of these behaviors. The importance of developmental factors in the determination of his behavior, and their significance in treatment planning, are discussed. Although the current definitions of conduct and substance use disorders are useful and valid, attention to individual contextual factors may enhance the clinical utility of these categories.

Identification of an interaction between SOX9 and HSP70

The campomelic dysplasia/autosomal sex reversal protein SOX9 is an important developmental transcription factor, required for correct bone and testis formation. Through in vitro and in vivo studies we have identified the heat shock protein HSP70 as an interacting partner for SOX9 in chondrocyte and testicular cell lines. HSP70 forms a ternary complex with DNA-bound SOX9. The interaction between HSP70 and SOX9 is ATP-independent and involves a highly conserved region of SOX9 hitherto of unknown function and the C-terminal region of HSP70. Our results implicate HSP70–SOX9 interactions in the assembly of multi-protein complexes during SOX9-mediated transcription.

Informatics Diffusion in South American Developing Economies

Lessons learned from the countries highlighted in this article suggest that appropriate transfer of informatics to developing countries requires a framework that uses the abundance of literature highlighting the relationship of informatics and economic development. The informatics issues that concern developing countries are those associated with operational and infrastructure problems. This study seeks to identify important developmental factors by considering the situation in three countries in South America.

Retinoic acid up-regulates ciliary neurotrophic factor receptors in cultured chick neurons and cardiomyocytes

Retinoic acid is an important developmental factor in the heart and nervous system and regulates the expression of trophic factor receptors in neural cell lines. Here we show the effects of retinoic acid on cytokine responsiveness in embryonic chick neurons and myocytes. Treatment of cultured cardiomyocytes and retinal and ciliary ganglion neurons with retinoic acid resulted in increased expression of receptors for the neuropoietic cytokine, CNTF. All- trans-retinoic acid induced as much as a 3-fold increase in CNTF receptor α subunit mRNA in a time and concentration dependent manner and resulted in an enhanced CNTF-induced tyrosine phosphorylation of the transcription factor, STAT3. These results indicate that neurons and myocytes expressing CNTF receptors are responsive to retinoic acid and suggest that retinoids may regulate cell sensitivity to cytokines during development.