Tpit-independent function of NeuroD1(BETA2) in pituitary corticotroph differentiation

Bruno Lamolet, Gino Poulin, Khoi Chu, François Guillemot, Ming Jer Tsai, Jacques Drouin

    Research output: Contribution to journalArticlepeer-review

    Abstract

    NeuroD1(BETA2) and Tpit are cell-specific activators of pituitary proopiomelanocortin (POMC) gene transcription. Expression of both factors slightly precedes that of POMC at embryonic d 12.5 of mouse pituitary development. We now report that NeuroD1(BETA2) is required for early corticotroph differentiation. In agreement with the transcriptional synergism observed between Tpit and basic helix-loop-helix dimers containing NeuroD1(BETA2), POMC expression is delayed in NeuroD1-deficient mice. However, this differentiation defect does not reflect a change of corticotroph commitment as revealed by Tpit expression. The delay of corticotroph terminal differentiation is transient and coincides with the developmental window of NeuroD1 expression in corticotrophs. In contrast to their requirement in other NeuroD1-expressing cells, the neurogenin genes do not appear to be necessary for corticotroph differentiation. Taken together with a similar requirement of Tpit for corticotroph differentiation but not for commitment, the present data indicate that the POMC promoter is a point of convergence for independent corticotroph differentiating signals.
    Original languageEnglish
    Pages (from-to)995-1003
    Number of pages8
    JournalMolecular Endocrinology
    Volume18
    Issue number4
    DOIs
    Publication statusPublished - Apr 2004

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