A5087013195- Congenital gastrointestinal and neural anomalies
- Gastrointestinal motility and disorders
- Intestinal Malrotation and Obstruction Disorders
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Neuropeptides and Animal Physiology
- Pain Mechanisms and Treatments
- Child Nutrition and Feeding Issues
- Pediatric Hepatobiliary Diseases and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Axon Guidance and Neuronal Signaling
- Eicosanoids and Hypertension Pharmacology
- Cholinesterase and Neurodegenerative Diseases
- Diet and metabolism studies
- Biochemical effects in animals
- Neurotransmitter Receptor Influence on Behavior
- Restless Legs Syndrome Research
- Anesthesia and Neurotoxicity Research
- Infant Nutrition and Health
- Congenital heart defects research
- Neurogenetic and Muscular Disorders Research
- Digestive system and related health
Columbia University
2007-2022
Columbia University Irving Medical Center
2006
Albert Einstein College of Medicine
1984-1992
Yeshiva University
1986-1989
John F. Kennedy Center for the Performing Arts
1986-1988
New York University
1984
Harvard University
1975-1980
Harvard University Press
1980
Cornell University
1980
National Institutes of Health
1974-1977
The gut contains a large 5-HT pool in enterochromaffin (EC) cells and smaller the enteric nervous system (ENS). During development, neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, calcitonin gene-related peptide-expressing essential for gastrointestinal motility. biosynthesis depends on tryptophan hydroxylase 1 (TPH1) EC TPH2 neurons; therefore, mice lacking...
The hypothesis that BMPs (bone morphogenetic proteins), which act early in gut morphogenesis, also regulate specification and differentiation the developing enteric nervous system (ENS) was tested. Expression of BMP-2 BMP-4, BMPR-IA (BMP receptor subunit), BMPR-IB, BMPR-II, BMP antagonists, noggin, gremlin, chordin, follistatin found when neurons first appear primordial bowel at embryonic day 12 (E12). Agonists, receptors, antagonists were detected separated populations neural crest-...
The effects of bone morphogenetic protein (BMP) signaling on enteric neuron development were examined in transgenic mice overexpressing either the BMP inhibitor, noggin, or BMP4 under control specific enolase (NSE) promoter. Noggin antagonism increased total numbers neurons and those subpopulations derived from precursors that exit cell cycle early neurogenesis (serotonin, calretinin, calbindin). In contrast, noggin overexpression decreased late (gamma-aminobutyric acid, tyrosine hydroxylase...
The precursor cells that form the enteric nervous system (ENS) are multipotent when they arrive in gut from neural crest. Their differentiation thus depends on signals microenvironment. Crest-derived were isolated fetal rat bowel by immunoselection at E14 with NC-1/HNK-1 antibodies and secondary coupled to magnetic beads. NC-1/HNK-1-immunoreactive enriched approximately 36-fold. NC-1/HNK-1-selected population residual plated equal cell density maintained a defined medium for 6-7 d. total...
Neurotrophin-3 (NT-3) promotes enteric neuronal development<i>in vitro</i>; nevertheless, an nervous system (ENS) is present in mice lacking NT-3 or TrkC. We thus analyzed the physiological significance of ENS development. Subsets neurons developing <i>in vitro</i> response to became dependent; withdrawal led apoptosis, selectively TrkC-expressing neurons. Antibodies NT-3, which blocked developmental crest-derived cells exogenous did not inhibit development cultures isolated but so mixed...
Neurotrophin-3 (NT-3) is known to promote enteric neuronal and glial development. Ciliary neurotrophic factor (CNTF) leukemia inhibitory (LIF) were investigated test the hypothesis that development of subsets neurons and/or glia also affected by a neuropoietic cytokine, itself, or together with NT-3. Crest-derived cells, immunoselected from fetal rat gut (E14) antibodies p75NTR, found RT-PCR immunocytochemistry (after culture) express both alpha (CNTER alpha) beta components (gp130 LIFR...
The effect of nerve growth factor (NGF) on the action potential sensory ganglion neurons was investigated in long-term organotypic cultures embryonic mouse dorsal root ganglia grown isolated or attached to spinal cord explants. present study demonstrates that NGF regulates a specific bioelectric property these neurons--the duration Ca2+ component somatic potential--at mature stages when they no longer require for survival. Prolonged culture fetal with relatively low levels shortens...
Abstract The neural crest–derived cells that colonize the fetal bowel become patterned into two ganglionated plexuses. hypothesis bone morphogenetic proteins (BMPs) promote ganglionation by regulating cell adhesion molecule (NCAM) polysialylation was tested. Transcripts encoding sialyltransferases, ST8Sia IV (PST) and II (STX), which polysialylate NCAM, were detectable in rat gut E12 but downregulated postnatally. PSA‐NCAM‐immunoreactive neuron numbers, not those of developmentally regulated...
Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal from embryonic sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high and synthesizes dopamine. These also have excitable membranes generate action potentials in response to electrical stimuli. Thus cells, generated by fusion nervous system, can acquire neural properties not...
Trophic factor signaling is important for the migration, differentiation, and survival of enteric neurons during development. The mechanisms that regulate maturation in postnatal life, however, are poorly understood. Here, we show transcriptional cofactor HIPK2 (homeodomain interacting protein kinase 2) required regulating gliogenesis Mice lacking display a spectrum gastrointestinal (GI) phenotypes, including distention colon slowed GI transit time. Although loss does not affect prenatal...
Cerebral dopamine neurotrophic factor (CDNF) is neuroprotective for nigrostriatal neurons and restores dopaminergic function in animal models of Parkinson's disease (PD). To understand the role CDNF mammals, we generated knockout mice (Cdnf-/-), which are viable, fertile, have a normal life-span. Surprisingly, an age-dependent loss enteric occurs selectively submucosal but not myenteric plexus. This neuronal consequence increased apoptosis neurodegeneration autophagy. Quantitatively,...
Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide that structurally homologous to epidermal (EGF) and appears bind the same receptor in all systems tested previously. In present study, TGF was found enhance survival neurite outgrowth of cultured neonatal rat dorsal root ganglion (DRG) neurons dose-dependent manner. This effect observed with concentrations as low 17.8 pM. By contrast, EGF at up 83 nM ineffective. Moreover, did not antagonize survival-promoting unless...
Past studies have shown that purine analogs block certain, but not all, responses of cultured rat PC12 pheochromocytoma cells to nerve growth factor (NGF). In the present work, newborn sympathetic and sensory neurons were exposed NGF in presence or absence 6-thioguanine 2-aminopurine. These compounds reversibly suppressed NGF-dependent neurite outgrowth by did so at concentrations comparable those effective on cells. contrast their effects neurites, neither compound significantly blocked...