The embryonic tectum displays an anteroposterior gradient in development and produces the superior colliculus and inferior colliculus. Studies suggest that partition of the tectum is controlled by different strengths and durations of FGF signals originated from the so-called isthmic organizer at the mid/hindbrain junction; however, the underlying mechanism is unclear. We show that deleting Ptpn11, which links FGF with the ERK pathway, prevents inferior colliculus formation by depleting a previously uncharacterized stem cell zone. The stem-zone loss is attributed to shortening of S phase and acceleration of cell cycle exit and neurogenesis. Expression of a constitutively active Mek1 (Mek1DD), the known ERK activator, restores the tectal stem zone and the inferior colliculus without Ptpn11. By contrast, Mek1DD expression fails to rescue the tectal stem zone and the inferior colliculus in the absence of Fgf8 and the isthmic organizer, indicating that FGF and Mek1DD initiate qualitatively and/or quantitatively distinctive signaling. Together, our data show that the formation of the inferior colliculus relies on the provision of new cells from the tectal stem zone. Furthermore, distinctive ERK signaling mediates Fgf8 in the control of cell survival, tissue polarity and cytogenetic gradient during the development of the tectum.
The authors declare no competing or financial interests.
A.D., K.L., X.H. and Q.G., performed experiments, analyzed data, discussed and commented on the written manuscript; A.D. helped write the manuscript; J.Y.H.L. conceived and directed the project, analyzed data and wrote the paper.
This work was supported by a grant from the National Institutes of Health [R01MH094914]. Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.138537.supplemental
- Received April 12, 2016.
- Accepted August 22, 2016.