PMID- 10331987
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 126
IP  - 12
DP  - 1999 Jun
TI  - Distinct signaling molecules control Hoxa-11 and Hoxa-13 expression in the muscle 
      precursor and mesenchyme of the chick limb bud.
PG  - 2771-83
AB  - The limb muscles, originating from the ventrolateral portion of the somites, 
      exhibit position-specific morphological development through successive splitting 
      and growth/differentiation of the muscle masses in a region-specific manner by 
      interacting with the limb mesenchyme and the cartilage elements. The molecular 
      mechanisms that provide positional cues to the muscle precursors are still 
      unknown. We have shown that the expression patterns of Hoxa-11 and Hoxa-13 are 
      correlated with muscle patterning of the limb bud (Yamamoto et al., 1998) and 
      demonstrated that muscular Hox genes are activated by signals from the limb 
      mesenchyme. We dissected the regulatory mechanisms directing the unique 
      expression patterns of Hoxa-11 and Hoxa-13 during limb muscle development. 
      HOXA-11 protein was detected in both the myogenic cells and the zeugopodal 
      mesenchymal cells of the limb bud. The earlier expression of HOXA-11 in both the 
      myogenic precursor cells and the mesenchyme was dependent on the apical 
      ectodermal ridge (AER), but later expression was independent of the AER. HOXA-11 
      expression in both myogenic precursor cells and mesenchyme was induced by 
      fibroblast growth factor (FGF) signal, whereas hepatocyte growth factor/scatter 
      factor (HGF/SF) maintained HOXA-11 expression in the myogenic precursor cells, 
      but not in the mesenchyme. The distribution of HOXA-13 protein expression in the 
      muscle masses was restricted to the posterior region. We found that HOXA-13 
      expression in the autopodal mesenchyme was dependent on the AER but not on the 
      polarizing region, whereas expression of HOXA-13 in the posterior muscle masses 
      was dependent on the polarizing region but not on the AER. Administration of 
      BMP-2 at the anterior margin of the limb bud induced ectopic HOXA-13 expression 
      in the anterior region of the muscle masses followed by ectopic muscle formation 
      close to the source of exogenous BMP-2. In addition, NOGGIN/CHORDIN, antagonists 
      of BMP-2 and BMP-4, downregulated the expression of HOXA-13 in the posterior 
      region of the muscle masses and inhibited posterior muscle development. These 
      results suggested that HOXA-13 expression in the posterior muscle masses is 
      activated by the posteriorizing signal from the posterior mesenchyme via BMP-2. 
      On the contrary, the expression of HOXA-13 in the autopodal mesenchyme was 
      affected by neither BMP-2 nor NOGGIN/CHORDIN. Thus, mesenchymal HOXA-13 
      expression was independent of BMP-2 from polarizing region, but was under the 
      control of as yet unidentified signals from the AER. These results showed that 
      expression of Hox genes is regulated differently in the limb muscle precursor and 
      mesenchymal cells.
FAU - Hashimoto, K
AU  - Hashimoto K
AD  - Division of Biological Science, Graduate School of Science, Nagoya University, 
      Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
FAU - Yokouchi, Y
AU  - Yokouchi Y
FAU - Yamamoto, M
AU  - Yamamoto M
FAU - Kuroiwa, A
AU  - Kuroiwa A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (homeobox protein HOXA13)
RN  - 148294-77-3 (noggin protein)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 93586-27-7 (chordin)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 2
MH  - Bone Morphogenetic Proteins/metabolism/pharmacology
MH  - COS Cells/metabolism
MH  - Carrier Proteins
MH  - Cell Transplantation
MH  - Chick Embryo
MH  - Ectoderm/physiology
MH  - Fibroblast Growth Factors/metabolism/pharmacology
MH  - Gene Expression Regulation, Developmental
MH  - *Glycoproteins
MH  - Hepatocyte Growth Factor/metabolism/pharmacology
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Limb Buds/*metabolism
MH  - Mesoderm/*metabolism
MH  - Muscle, Skeletal/cytology/*embryology/metabolism
MH  - Proteins/genetics/metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Signal Transduction
MH  - *Transforming Growth Factor beta
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - 10.1242/dev.126.12.2771 [doi]
PST - ppublish
SO  - Development. 1999 Jun;126(12):2771-83. doi: 10.1242/dev.126.12.2771.