PMID- 10556075
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20081121
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 126
IP  - 23
DP  - 1999 Dec
TI  - The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed
      cell death in the developing limb.
PG  - 5515-22
AB  - In this study, we have analyzed the expression and function of Gremlin in the
      developing avian limb. Gremlin is a member of the DAN family of BMP antagonists
      highly conserved through evolution able to bind and block BMP2, BMP4 and BMP7. At
      early stages of development, gremlin is expressed in the dorsal and ventral
      mesoderm in a pattern complementary to that of bmp2, bmp4 and bmp7. The
      maintenance of gremlin expression at these stages is under the control of the
      AER, ZPA, and BMPs. Exogenous administration of recombinant Gremlin indicates
      that this protein is involved in the control of limb outgrowth. This function
      appears to be mediated by the neutralization of BMP function to maintain an
      active AER, to restrict the extension of the areas of programmed cell death and
      to confine chondrogenesis to the central core mesenchyme of the bud. At the
      stages of digit formation, gremlin is expressed in the proximal boundary of the
      interdigital mesoderm of the chick autopod. The anti-apoptotic influence of
      exogenous Gremlin, which results in the formation of soft tissue syndactyly in
      the chick, together with the expression of gremlin in the duck interdigital webs,
      indicates that Gremlin regulates the regression of the interdigital tissue. At
      later stages of limb development, gremlin is expressed in association with the
      differentiating skeletal pieces, muscles and the feather buds. The different
      expression of Gremlin in relation with other BMP antagonists present in the limb 
      bud, such as Noggin, Chordin and Follistatin indicates that the functions of BMPs
      are regulated specifically by the different BMP antagonists, acting in a
      complementary fashion rather than being redundant signals.
FAU - Merino, R
AU  - Merino R
AD  - Unidad de Investigacion, Hospital Universitario Marques de Valdecilla, Santander 
      39008, Spain.
FAU - Rodriguez-Leon, J
AU  - Rodriguez-Leon J
FAU - Macias, D
AU  - Macias D
FAU - Ganan, Y
AU  - Ganan Y
FAU - Economides, A N
AU  - Economides AN
FAU - Hurle, J M
AU  - Hurle JM
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 Protein 4)
RN  - 0 (Bone Morphogenetic Protein 7)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fibroblast Growth Factor 4)
RN  - 0 (Follistatin)
RN  - 0 (Glycoproteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (MSX2 protein)
RN  - 0 (MyoD Protein)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 148294-77-3 (noggin protein)
RN  - 148997-75-5 (Fibroblast Growth Factor 8)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 93586-27-7 (chordin)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Bone Morphogenetic Protein 2
MH  - Bone Morphogenetic Protein 4
MH  - Bone Morphogenetic Protein 7
MH  - Bone Morphogenetic Proteins/genetics/*metabolism
MH  - Carrier Proteins
MH  - Chick Embryo
MH  - Chondrogenesis/*physiology
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Ectoderm/metabolism
MH  - Fibroblast Growth Factor 4
MH  - Fibroblast Growth Factor 8
MH  - Fibroblast Growth Factors/genetics/metabolism
MH  - Follistatin
MH  - *Gene Expression Regulation, Developmental
MH  - Glycoproteins/genetics/metabolism
MH  - Hedgehog Proteins
MH  - Homeodomain Proteins
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Limb Buds
MH  - Mesoderm
MH  - MyoD Protein/genetics/metabolism
MH  - Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - *Trans-Activators
MH  - *Transforming Growth Factor beta
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
PST - ppublish
SO  - Development. 1999 Dec;126(23):5515-22.