PUBLICATION
Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer
- Authors
- O'Hara, F.P., Beck, E., Barr, L.K., Wong, L.L., Kessler, D.S., and Riddle, R.D.
- ID
- ZDB-PUB-050610-13
- Date
- 2005
- Source
- Development (Cambridge, England) 132(14): 3163-3173 (Journal)
- Registered Authors
- Wong, Lily
- Keywords
- Isthmus, Lmx1b, Mesencephalon, Metencephalon, Pax, Wnt, Zebrafish
- MeSH Terms
-
- LIM-Homeodomain Proteins
- Amino Acid Sequence
- Zebrafish/embryology*
- Zebrafish/genetics
- Homeodomain Proteins/genetics
- Homeodomain Proteins/physiology*
- Mesencephalon/embryology*
- DNA-Binding Proteins/metabolism
- PAX2 Transcription Factor
- Gene Expression Regulation, Developmental/physiology
- Wnt1 Protein
- Fibroblast Growth Factor 8
- Animals
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Transcription Factors/physiology*
- Wnt Proteins
- Zebrafish Proteins
- Metencephalon/embryology*
- Protein Isoforms/genetics
- Protein Isoforms/physiology
- Fibroblast Growth Factors/genetics
- Fibroblast Growth Factors/metabolism
- Molecular Sequence Data
- Intercellular Signaling Peptides and Proteins/biosynthesis
- Intercellular Signaling Peptides and Proteins/genetics
- PubMed
- 15944182 Full text @ Development
Citation
O'Hara, F.P., Beck, E., Barr, L.K., Wong, L.L., Kessler, D.S., and Riddle, R.D. (2005) Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. Development (Cambridge, England). 132(14):3163-3173.
Abstract
The mesencephalic and metencephalic region (MMR) of the vertebrate central nervous system develops in response to signals produced by the isthmic organizer (IsO). We have previously reported that the LIM homeobox transcription factor Lmx1b is expressed within the chick IsO, where it is sufficient to maintain expression of the secreted factor wnt1. In this paper, we show that zebrafish express two Lmx1b orthologs, lmx1b.1 and lmx1b.2, in the rostral IsO, and demonstrate that these genes are necessary for key aspects of MMR development. Simultaneous knockdown of Lmx1b.1 and Lmx1b.2 using morpholino antisense oligos results in a loss of wnt1, wnt3a, wnt10b, pax8 and fgf8 expression at the IsO, leading ultimately to programmed cell death and the loss of the isthmic constriction and cerebellum. Single morpholino knockdown of either Lmx1b.1 or Lmx1b.2 has no discernible effect on MMR development. Maintenance of lmx1b.1 and lmx1b.2 expression at the isthmus requires the function of no isthmus/pax2.1, as well as Fgf signaling. Transient misexpression of Lmx1b.1 or Lmx1b.2 during early MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as throughout much of the embryo. We propose that Lmx1b.1- and Lmx1b.2-mediated regulation of wnt1, wnt3a, wnt10b, pax8 and fgf8 maintains cell survival in the isthmocerebellar region.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping