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Development of neuroendocrine lineages requires the bHLH–PAS transcription factor SIM1
- Publication Year :
- 1998
- Publisher :
- Cold Spring Harbor Laboratory Press, 1998.
-
Abstract
- The bHLH–PAS transcription factor SIM1 is expressed during the development of the hypothalamic–pituitary axis in three hypothalamic nuclei: the paraventricular nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic nucleus (SON). To investigateSim1 function in the hypothalamus, we produced mice carrying a null allele of Sim1 by gene targeting. Homozygous mutant mice die shortly after birth. Histological analysis shows that the PVN and the SON of these mice are hypocellular. At least five distinct types of secretory neurons, identified by the expression of oxytocin, vasopressin, thyrotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin, are absent in the mutant PVN, aPV, and SON. Moreover, we show that SIM1 controls the development of these secretory neurons at the final stages of their differentiation. A subset of these neuronal lineages in the PVN/SON are also missing in mice bearing a mutation in the POU transcription factor BRN2. We provide evidence that, during development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails to express Brn2. Our results strongly indicate that SIM1 functions upstream to maintain Brn2 expression, which in turn directs the terminal differentiation of specific neuroendocrine lineages within the PVN/SON.
- Subjects :
- Male
medicine.medical_specialty
Vasopressin
endocrine system
Molecular Sequence Data
Hypothalamus
Mice, Transgenic
Biology
Supraoptic nucleus
Mice
Internal medicine
Genetics
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
Cell Lineage
Amino Acid Sequence
Transcription factor
Homeodomain Proteins
Neurons
POU domain
digestive, oral, and skin physiology
Helix-Loop-Helix Motifs
Cell Differentiation
Null allele
Neurosecretory Systems
DNA-Binding Proteins
Mice, Inbred C57BL
Repressor Proteins
Endocrinology
Somatostatin
nervous system
POU Domain Factors
SIM1
Female
Supraoptic Nucleus
hormones, hormone substitutes, and hormone antagonists
Developmental Biology
Research Paper
Paraventricular Hypothalamic Nucleus
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f361af7a43b52106c6c90c56bb1981e2