Mcrs1 interacts with Six1 to influence early craniofacial and otic development.

Mcrs1 interacts with Six1 to influence early craniofacial and otic development.
Dev Biol. 2020 Sep 03;:
Authors: Neilson KM, Keer S, Bousquet N, Macrorie O, Majumdar HD, Kenyon KL, Alfandari D, Moody SA
Abstract
The Six1 transcription factor plays a major role in craniofacial development. Mutations in SIX1 and its co-factor, EYA1, are causative for about 50% of Branchio-otic/Branchio-oto-renal syndrome (BOR) patients, who are characterized by variable craniofacial, otic and renal malformations. We previously screened for other proteins that might interact with Six1 to identify additional genes that may play a role in BOR, and herein characterize the developmental role of one of them, Microspherule protein 1 (Mcrs1). We found that in cultured cells, Mcrs1 bound to Six1 and in both cultured cells and embryonic ectoderm reduced Six1-Eya1 transcriptional activation. Knock-down of Mcrs1 in embryos caused an expansion of the domains of neural plate genes and two genes expressed in both the neural plate and neural crest (zic1, zic2). In contrast, two other genes expressed in pre-migratory neural crest (foxd3, sox9) were primarily reduced. Cranial placode genes showed a mixture of expanded and diminished expression domains. At larval stages, loss of Mcrs1 resulted in a significant reduction of otic vesicle gene expression concomitant with a smaller otic vesicle volume. Experimentally increasing Mcrs1 above endogenous levels favored the expan...

Source: Developmental Biology - September 2, 2020 Category: Biology Authors: Neilson KM, Keer S, Bousquet N, Macrorie O, Majumdar HD, Kenyon KL, Alfandari D, Moody SA Tags: Dev Biol Source Type: research