We have characterised the functions of the bHLH transcriptional repressors HES1 and HES5 in neurogenesis, using the development of the olfactory placodes in mouse embryos as a model. Hes1 and Hes5 are expressed with distinct patterns in the olfactory placodes and are subject to different regulatory mechanisms. Hes1 is expressed in a broad placodal domain, which is maintained in absence of the neural determination gene Mash1. In contrast, expression of Hes5 is restricted to clusters of neural progenitor cells and requires Mash1 function. Mutations in Hes1 and Hes5 also have distinct consequences on olfactory placode neurogenesis. Loss of Hes1 function leads both to expression of Mash1 outside of the normal domain of neurogenesis and to increased density of MASH1-positive progenitors within this domain, and results in an excess of neurons after a delay. A mutation in Hes5 does not produce any apparent defect. However, olfactory placodes that are double mutant for Hes1 and Hes5 upregulate Ngn1, a neural bHLH gene activated downstream of Mash1, and show a strong and rapid increase in neuronal density. Together, our results suggest that Hes1 regulates Mash1 transcription in the olfactory placode in two different contexts, initially as a prepattern gene defining the placodal domain undergoing neurogenesis and, subsequently, as a neurogenic gene controlling the density of neural progenitors in this domain. Hes5 synergizes with Hes1 and regulates neurogenesis at the level of Ngn1 expression. Therefore, the olfactory sensory neuron lineage is regulated at several steps by negative signals acting through different Hes genes and targeting the expression of different proneural gene homologs.
Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium
E. Cau, G. Gradwohl, S. Casarosa, R. Kageyama, F. Guillemot; Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development 1 June 2000; 127 (11): 2323–2332. doi: https://doi.org/10.1242/dev.127.11.2323
Download citation file:
Advertisement
Cited by
Development Journal Meeting 2022: From Stem Cells to Human Development
-JournalMeeting.png?versionId=3939)
Following a virtual meeting in 2020, we are delighted to announce that the fifth iteration of our popular Journal Meeting will be held from 11-14 September 2022 at the historic Wotton House, Surrey. Registration is open now.
Preprints in Development
(update)-InPreprints.png?versionId=3939)
As part of our efforts to support the use of preprints and help curate the preprint literature, we are delighted to launch a new article type: ‘In preprints’. These pieces will discuss one or more recent preprints and place them in a broader context.
Submit your next Techniques and Resources paper to Development
-TechniquesAndResources.png?versionId=3939)
Development regularly publishes Techniques and Resources papers. These manuscripts describe a novel technique, a substantial advance of an existing technique, or a new resource that will have a significant impact on developmental biology research. Find out more here.
Transitions in development: Rashmi Priya
(update)-RashmiPriya.png?versionId=3939)
Rashmi Priya’s research group uses the zebrafish heart as a model system to understand the complex morphogenetic events of organogenesis. We interviewed Rashmi to learn about her career path so far, and to discuss the challenges of starting a lab in the middle of a global pandemic.
The Node Network
-NodeNetwork.png?versionId=3939)
The Node Network is a global directory of developmental and stem cell biologists, designed to help you find speakers, referees, panel members and potential collaborators. Find out more about the Node Network.