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J Neurosci. 2014 Sep 10;34(37):12527-37. doi: 10.1523/JNEUROSCI.1330-14.2014.

Wls provides a new compartmental view of the rhombic lip in mouse cerebellar development.

Author information

1
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and.
2
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
3
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z4H4 and Dang@cmmt.ubc.ca.

Abstract

Math1 is the defining molecule of the cerebellar rhombic lip and Pax6 is downstream in the Math1 pathway. In the present study, we discover that Wntless (Wls) is a novel molecular marker of the cells in the interior face of the rhombic lip throughout normal mouse cerebellar development. Wls expression is found complementary to the expression of Math1 and Pax6, which are localized to the exterior face of the rhombic lip. To determine the interaction between these molecules, we examine the loss-of-Math1 or loss-of-Pax6 in the cerebellum, i.e., the Math1-null and Pax6-null (Sey) mutant cerebella. The presence of Wls-positive cells in the Math1-null rhombic lip indicates that Wls expression is independent of Math1. In the Sey mutant cerebellum, there is an expansion of Wls-expressing cells into regions that are normally colonized by Pax6-expressing cells. The ectopic expression of Wls in the Pax6-null cerebellum suggests a negative interaction between Wls-expressing cells and Pax6-positive cells. These findings suggest that the rhombic lip is dynamically patterned by the expression of Wls, Math1, and Pax6. We also examine five rhombic lip cell markers (Wls, Math1, Pax6, Lmx1a, and Tbr2) to identify four molecularly distinct compartments in the rhombic lip during cerebellar development. The existence of spatial compartmentation in the rhombic lip and the interplay between Wls, Math1, and Pax6 in the rhombic lip provides novel views of early cerebellar development.

KEYWORDS:

Pax6; Wls; cerebellar compartments; cerebellum; developmental biology; rhombic lip

PMID:
25209290
PMCID:
PMC4160781
DOI:
10.1523/JNEUROSCI.1330-14.2014
[Indexed for MEDLINE]
Free PMC Article

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