Chordin: Difference between revisions

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(Category:Vertebrate developmental biology)
 
imported>Melchior Philips
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'''Chordin''' is a [[bone morphogenetic protein]] [[antagonist]] composed of four small cysteine-rich domains, whose function is not known. Chordin was originally identified in [[Xenopus laevis]] in the laboratory of [[Edward M. De Robertis]] as a key developmental [[protein]] that dorsalizes early [[vertebrate]] embryonic tissues.<ref name="pmid8001117">{{cite journal |vauthors=Sasai Y, Lu B, Steinbeisser H, Geissert D, Gont LK, De Robertis EM | title = Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes | journal = Cell | volume = 79 | issue = 5 | pages = 779–90 |date=December 1994 | pmid = 8001117 | pmc = 3082463 | doi =10.1016/0092-8674(94)90068-X }}</ref> The [[polypeptide]] is 941 amino acids long and 120 kDa large<ref name="pmid10648240">{{cite journal |vauthors=Larraín J, Bachiller D, Lu B, Agius E, Piccolo S, De Robertis EM | title = BMP-binding modules in chordin: a model for signalling regulation in the extracellular space | journal = Development | volume = 127 | issue = 4 | pages = 821–30 |date=February 2000 | pmid = 10648240 | pmc = 2280033 | doi = }}</ref> and it [[dorsum (biology)|dorsalizes]] the developing [[embryo]] by binding ventralizing [[TGFβ]] proteins such as [[bone morphogenetic protein]]s.<ref name="pmid9782094">{{cite journal |vauthors=Pappano WN, Scott IC, Clark TG, Eddy RL, Shows TB, Greenspan DS | title = Coding sequence and expression patterns of mouse chordin and mapping of the cognate mouse chrd and human CHRD genes | journal = Genomics | volume = 52 | issue = 2 | pages = 236–9 |date=September 1998 | pmid = 9782094 | doi = 10.1006/geno.1998.5474 | url =  }}</ref> It may also play a role in [[organogenesis]]. There are five named [[isoform]]s of this protein that are produced by [[alternative splicing]].<ref name="pmid11472837">{{cite journal |vauthors=Millet C, Lemaire P, Orsetti B, Guglielmi P, François V | title = The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities | journal = Mech. Dev. | volume = 106 | issue = 1–2 | pages = 85–96 |date=August 2001 | pmid = 11472837 | doi = 10.1016/S0925-4773(01)00423-3 }}</ref>
 
'''Chordin''' is a [[bone morphogenetic protein]] [[antagonist]] composed of four small cysteine-rich domains, whose function is not known. In humans, the chordin peptide is encoded by the ''CHRD'' [[gene]].<ref name="pmid10480362">{{cite journal |vauthors=Smith M, Herrell S, Lusher M, Lako L, Simpson C, Wiestner A, Skoda R, Ireland M, Strachan T | title = Genomic organisation of the human chordin gene and mutation screening of candidate Cornelia de Lange syndrome genes | journal = Hum. Genet. | volume = 105 | issue = 1–2 | pages = 104–11 | year = 1999 | pmid = 10480362 | doi = 10.1007/s004390051070 }}</ref>
 
== History ==
 
Chordin was originally identified in the [[African clawed frog]] (''Xenopus laevis'') in the laboratory of [[Edward M. De Robertis]] as a key developmental [[protein]] that dorsalizes early [[vertebrate]] embryonic tissues.<ref name="pmid8001117">{{cite journal |vauthors=Sasai Y, Lu B, Steinbeisser H, Geissert D, Gont LK, De Robertis EM | title = Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes | journal = Cell | volume = 79 | issue = 5 | pages = 779–90 |date=December 1994 | pmid = 8001117 | pmc = 3082463 | doi =10.1016/0092-8674(94)90068-X }}</ref>
 
== Structure ==
The Chordin [[polypeptide]] is 941 amino acids long and 120 kDa large<ref name="pmid10648240">{{cite journal |vauthors=Larraín J, Bachiller D, Lu B, Agius E, Piccolo S, De Robertis EM | title = BMP-binding modules in chordin: a model for signalling regulation in the extracellular space | journal = Development | volume = 127 | issue = 4 | pages = 821–30 |date=February 2000 | pmid = 10648240 | pmc = 2280033 | doi = }}</ref>. There are five named [[isoform]]s of this protein that are produced by [[alternative splicing]].<ref name="pmid11472837">{{cite journal |vauthors=Millet C, Lemaire P, Orsetti B, Guglielmi P, François V | title = The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities | journal = Mech. Dev. | volume = 106 | issue = 1–2 | pages = 85–96 |date=August 2001 | pmid = 11472837 | doi = 10.1016/S0925-4773(01)00423-3 }}</ref>
 
== Function ==
It [[dorsum (biology)|dorsalizes]] the developing [[embryo]] by binding ventralizing [[TGFβ]] proteins such as [[bone morphogenetic protein]]s.<ref name="pmid9782094">{{cite journal |vauthors=Pappano WN, Scott IC, Clark TG, Eddy RL, Shows TB, Greenspan DS | title = Coding sequence and expression patterns of mouse chordin and mapping of the cognate mouse chrd and human CHRD genes | journal = Genomics | volume = 52 | issue = 2 | pages = 236–9 |date=September 1998 | pmid = 9782094 | doi = 10.1006/geno.1998.5474 | url =  }}</ref> It may also play a role in [[organogenesis]].


In mice, Chordin is expressed in the node but not in the anterior visceral [[endoderm]]. It has been found to be required for [[forebrain]] development.<ref name="pmid10688202">{{cite journal |vauthors=Bachiller D, Klingensmith J, Kemp C, Belo JA, Anderson RM, May SR, McMahon JA, McMahon AP, Harland RM, Rossant J, De Robertis EM | title = The organizer factors Chordin and Noggin are required for mouse forebrain development | journal = Nature | volume = 403 | issue = 6770 | pages = 658–61 |date=February 2000 | pmid = 10688202 | doi = 10.1038/35001072 }}</ref> In developing mice that are deficient in both chordin and [[noggin (protein)|noggin]], the head is nearly absent. This is significant because when only noggin is deficient there are mild defects but the head still forms.<ref name="isbn0-12-374539-X">{{cite book |vauthors=Harris WA, Sanes DH, Reh TA | title = Development of the Nervous System | edition = Third | publisher = Academic Press | location = Boston | year = 2011 | page = 15 | isbn = 0-12-374539-X }}</ref>
In mice, Chordin is expressed in the node but not in the anterior visceral [[endoderm]]. It has been found to be required for [[forebrain]] development.<ref name="pmid10688202">{{cite journal |vauthors=Bachiller D, Klingensmith J, Kemp C, Belo JA, Anderson RM, May SR, McMahon JA, McMahon AP, Harland RM, Rossant J, De Robertis EM | title = The organizer factors Chordin and Noggin are required for mouse forebrain development | journal = Nature | volume = 403 | issue = 6770 | pages = 658–61 |date=February 2000 | pmid = 10688202 | doi = 10.1038/35001072 }}</ref> In developing mice that are deficient in both chordin and [[noggin (protein)|noggin]], the head is nearly absent. This is significant because when only noggin is deficient there are mild defects but the head still forms.<ref name="isbn0-12-374539-X">{{cite book |vauthors=Harris WA, Sanes DH, Reh TA | title = Development of the Nervous System | edition = Third | publisher = Academic Press | location = Boston | year = 2011 | page = 15 | isbn = 0-12-374539-X }}</ref>


In humans, the chordin peptide is encoded by the ''CHRD'' [[gene]].<ref name="pmid10480362">{{cite journal |vauthors=Smith M, Herrell S, Lusher M, Lako L, Simpson C, Wiestner A, Skoda R, Ireland M, Strachan T | title = Genomic organisation of the human chordin gene and mutation screening of candidate Cornelia de Lange syndrome genes | journal = Hum. Genet. | volume = 105 | issue = 1–2 | pages = 104–11 | year = 1999 | pmid = 10480362 | doi = 10.1007/s004390051070 }}</ref>
Chordin is also involved in avian [[gastrulation]].  It is expressed in the anterior cells of [[Koller's sickle]], which form the anterior cells of the [[primitive streak]], a key structure through which gastrulation occurs.<ref name=Vasiev>{{cite journal | last1 = Vasiev | first1 = B | last2 = Balter | first2 = A | last3 = Chaplain | first3 = M | last4 = Glazier | first4 = JA | last5 = Weijer | first5 = CJ | year = 2010 | title = Modeling gastrulation in the chick embryo: formation of the primitive streak | doi=10.1371/journal.pone.0010571 | journal = PLOS ONE | volume = 5 | issue = | page = e10571 | pmid=20485500 | pmc=2868022}}</ref>
 
Chordin is also involved in avian gastrulation.  It is expressed in the anterior cells of [[Koller's sickle]], which form the anterior cells of the [[primitive streak]], a key structure through which gastrulation occurs.<ref name=Vasiev>{{cite journal | last1 = Vasiev | first1 = B | last2 = Balter | first2 = A | last3 = Chaplain | first3 = M | last4 = Glazier | first4 = JA | last5 = Weijer | first5 = CJ | year = 2010 | title = Modeling gastrulation in the chick embryo: formation of the primitive streak | doi=10.1371/journal.pone.0010571 | journal = PLOS ONE | volume = 5 | issue = | page = e10571 | pmid=20485500 | pmc=2868022}}</ref>


== References ==
== References ==

Latest revision as of 10:58, 5 September 2018

CHRD domain
Identifiers
SymbolCHRD
PfamPF07452
InterProIPR010895
SMARTSM00754
PROSITEPS50933
chordin
Identifiers
SymbolCHRD
Entrez8646
HUGO1949
OMIM603475
RefSeqNM_003741
UniProtQ9H2X0
Other data
LocusChr. 3 q27

Chordin is a bone morphogenetic protein antagonist composed of four small cysteine-rich domains, whose function is not known. In humans, the chordin peptide is encoded by the CHRD gene.[1]

History

Chordin was originally identified in the African clawed frog (Xenopus laevis) in the laboratory of Edward M. De Robertis as a key developmental protein that dorsalizes early vertebrate embryonic tissues.[2]

Structure

The Chordin polypeptide is 941 amino acids long and 120 kDa large[3]. There are five named isoforms of this protein that are produced by alternative splicing.[4]

Function

It dorsalizes the developing embryo by binding ventralizing TGFβ proteins such as bone morphogenetic proteins.[5] It may also play a role in organogenesis.

In mice, Chordin is expressed in the node but not in the anterior visceral endoderm. It has been found to be required for forebrain development.[6] In developing mice that are deficient in both chordin and noggin, the head is nearly absent. This is significant because when only noggin is deficient there are mild defects but the head still forms.[7]

Chordin is also involved in avian gastrulation. It is expressed in the anterior cells of Koller's sickle, which form the anterior cells of the primitive streak, a key structure through which gastrulation occurs.[8]

References

  1. ↑ Smith M, Herrell S, Lusher M, Lako L, Simpson C, Wiestner A, Skoda R, Ireland M, Strachan T (1999). "Genomic organisation of the human chordin gene and mutation screening of candidate Cornelia de Lange syndrome genes". Hum. Genet. 105 (1–2): 104–11. doi:10.1007/s004390051070. PMID 10480362.
  2. ↑ Sasai Y, Lu B, Steinbeisser H, Geissert D, Gont LK, De Robertis EM (December 1994). "Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes". Cell. 79 (5): 779–90. doi:10.1016/0092-8674(94)90068-X. PMC 3082463. PMID 8001117.
  3. ↑ Larraín J, Bachiller D, Lu B, Agius E, Piccolo S, De Robertis EM (February 2000). "BMP-binding modules in chordin: a model for signalling regulation in the extracellular space". Development. 127 (4): 821–30. PMC 2280033. PMID 10648240.
  4. ↑ Millet C, Lemaire P, Orsetti B, Guglielmi P, François V (August 2001). "The human chordin gene encodes several differentially expressed spliced variants with distinct BMP opposing activities". Mech. Dev. 106 (1–2): 85–96. doi:10.1016/S0925-4773(01)00423-3. PMID 11472837.
  5. ↑ Pappano WN, Scott IC, Clark TG, Eddy RL, Shows TB, Greenspan DS (September 1998). "Coding sequence and expression patterns of mouse chordin and mapping of the cognate mouse chrd and human CHRD genes". Genomics. 52 (2): 236–9. doi:10.1006/geno.1998.5474. PMID 9782094.
  6. ↑ Bachiller D, Klingensmith J, Kemp C, Belo JA, Anderson RM, May SR, McMahon JA, McMahon AP, Harland RM, Rossant J, De Robertis EM (February 2000). "The organizer factors Chordin and Noggin are required for mouse forebrain development". Nature. 403 (6770): 658–61. doi:10.1038/35001072. PMID 10688202.
  7. ↑ Harris WA, Sanes DH, Reh TA (2011). Development of the Nervous System (Third ed.). Boston: Academic Press. p. 15. ISBN 0-12-374539-X.
  8. ↑ Vasiev, B; Balter, A; Chaplain, M; Glazier, JA; Weijer, CJ (2010). "Modeling gastrulation in the chick embryo: formation of the primitive streak". PLOS ONE. 5: e10571. doi:10.1371/journal.pone.0010571. PMC 2868022. PMID 20485500.
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