Aujla Paven K, Bogdanovic Vedran, Naratadam George T, Raetzman Lori T
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Dev Dyn. 2015 Aug;244(8):921-34. doi: 10.1002/dvdy.24283.
As the pituitary gland develops, signals from the hypothalamus are necessary for pituitary induction and expansion. Little is known about the control of cues that regulate early signaling between the two structures. Ligands and receptors of the Notch signaling pathway are found in both the hypothalamus and Rathke's pouch. The downstream Notch effector gene Hes1 is required for proper pituitary formation; however, these effects could be due to the action of Hes1 in the hypothalamus, Rathke's pouch, or both. To determine the contribution of hypothalamic Notch signaling to pituitary organogenesis, we used mice with loss and gain of Notch function within the developing hypothalamus.
We demonstrate that loss of Notch signaling by conditional deletion of Rbpj in the hypothalamus does not affect expression of Hes1 within the posterior hypothalamus or expression of Hes5. In contrast, expression of activated Notch within the hypothalamus results in ectopic Hes5 expression and increased Hes1 expression, which is sufficient to disrupt pituitary development and postnatal expansion.
Taken together, our results indicate that Rbpj-dependent Notch signaling within the developing hypothalamus is not necessary for pituitary development, but persistent Notch signaling and ectopic Hes5 expression in hypothalamic progenitors affects pituitary induction and expansion.
随着垂体的发育，来自下丘脑的信号对于垂体的诱导和扩展是必需的。关于调节这两个结构之间早期信号传导的线索的控制知之甚少。Notch信号通路的配体和受体在下丘脑和拉特克囊均有发现。下游Notch效应基因Hes1是垂体正常形成所必需的；然而，这些作用可能是由于Hes1在下丘脑、拉特克囊或两者中的作用。为了确定下丘脑Notch信号对垂体器官发生的贡献，我们使用了在发育中的下丘脑中Notch功能缺失和增加的小鼠。
我们证明，通过条件性缺失下丘脑中的Rbpj来缺失Notch信号，并不影响下丘脑后部Hes1的表达或Hes5的表达。相反，下丘脑内活化Notch的表达导致异位Hes5表达和Hes1表达增加，这足以破坏垂体发育和出生后扩展。
综上所述，我们的结果表明，发育中的下丘脑中依赖Rbpj的Notch信号对于垂体发育不是必需的，但下丘脑祖细胞中持续的Notch信号和异位Hes5表达会影响垂体诱导和扩展。
