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Development of neuroendocrine lineages requires the bHLH–PAS transcription factor SIM1

Open access
Michaud, Jacques L., Rosenquist, Thomas, May, Noah R., Fan, Chen-Ming·1998·Genes & Development

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 investigate Sim1 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.

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Metadata

Authors
Michaud, J. L., Rosenquist, T., May, N. R., & Fan, C.-M.
Venue
Genes & Development
Published
1998-10-15
Volume
12
Issue
20
Pages
3264-3275
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2141166900
Cited by
392
References
8
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: Development of neuroendocrine lineages requires the bHLH–PAS transcription factor SIM1. https://app.cochat.ai/papers/10.1101/gad.12.20.3264
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Michaud, J. L., Rosenquist, T., May, N. R., & Fan, C.-M. (1998). Development of neuroendocrine lineages requires the bHLH–PAS transcription factor SIM1. Genes & Development. https://doi.org/10.1101/gad.12.20.3264

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