Limb-patterning activity and restricted posterior localization of the amino-terminal product of Sonic hedgehog cleavage - PubMed (original) (raw)
Limb-patterning activity and restricted posterior localization of the amino-terminal product of Sonic hedgehog cleavage
A López-Martínez et al. Curr Biol. 1995.
Free article
Abstract
Background: Sonic hedgehog (Shh), a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh), has been implicated in patterning of the developing chick limb. Such a role is suggested by the restricted expression of Shh along the posterior limb bud margin, and by the observation that heterologous cells expressing Shh have limb-polarizing activity resembling that of cells from the polarizing region of the posterior limb bud margin. It has not been demonstrated, however, that the Sonic hedgehog protein (SHH) alone is sufficient for limb patterning. SHH has been shown to undergo autoproteolytic cleavage in vitro, yielding two smaller products. It is of interest, therefore, to determine whether processing of SHH occurs in the developing limb and how such processing influences the function of SHH.
Results: We demonstrate that SHH is proteolytically processed in developing chick limbs. Grafts of cells expressing SHH protein variants that correspond to individual cleavage products demonstrate that the ability to induce patterned gene expression and to impose morphological pattern upon the limb bud is limited to the amino-terminal product (SHH-N) of SHH proteolytic cleavage. We also demonstrate that bacterially synthesized and purified SHH-N, released from implanted beads, is sufficient for limb-patterning activity. Finally, we show that the endogenous amino-terminal cleavage product is tightly localized to the posterior margin of the limb bud.
Conclusions: Our data show that, of the two cleavage products resulting from SHH autoproteolysis, SHH-N expressed in grafted heterologous cells or supplied in purified form is sufficient to impose pattern upon the developing limb. Moreover, the restricted localization of the endogenous amino-terminal SHH cleavage product to the posterior border of the chick limb bud makes it unlikely that its patterning activity results from it being distributed in a broad gradient across the antero-posterior axis. More consistent with the observed localization is a model in which the amino-terminal SHH cleavage product exerts its patterning effects by local induction in or near the polarizing region, initiating a cascade of gene expression that ultimately extends across the developing limb.
Similar articles
- Sonic hedgehog (SHH) specifies muscle pattern at tissue and cellular chick level, in the chick limb bud.
Duprez D, Lapointe F, Edom-Vovard F, Kostakopoulou K, Robson L. Duprez D, et al. Mech Dev. 1999 Apr;82(1-2):151-63. doi: 10.1016/s0925-4773(99)00040-4. Mech Dev. 1999. PMID: 10354479 - Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta3) limb buds: their relationships in the signalling cascade involved in limb patterning.
Francis-West PH, Robertson KE, Ede DA, Rodriguez C, Izpisúa-Belmonte JC, Houston B, Burt DW, Gribbin C, Brickell PM, Tickle C. Francis-West PH, et al. Dev Dyn. 1995 Jun;203(2):187-97. doi: 10.1002/aja.1002030207. Dev Dyn. 1995. PMID: 7655081 - Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.
Chiang C, Litingtung Y, Harris MP, Simandl BK, Li Y, Beachy PA, Fallon JF. Chiang C, et al. Dev Biol. 2001 Aug 15;236(2):421-35. doi: 10.1006/dbio.2001.0346. Dev Biol. 2001. PMID: 11476582 - How the embryo makes a limb: determination, polarity and identity.
Tickle C. Tickle C. J Anat. 2015 Oct;227(4):418-30. doi: 10.1111/joa.12361. Epub 2015 Aug 7. J Anat. 2015. PMID: 26249743 Free PMC article. Review. - Mechanisms of limb patterning.
Johnson RL, Riddle RD, Tabin CJ. Johnson RL, et al. Curr Opin Genet Dev. 1994 Aug;4(4):535-42. doi: 10.1016/0959-437x(94)90069-f. Curr Opin Genet Dev. 1994. PMID: 7950321 Review.
Cited by
- Patterning of the Drosophila retina by the morphogenetic furrow.
Warren J, Kumar JP. Warren J, et al. Front Cell Dev Biol. 2023 Apr 6;11:1151348. doi: 10.3389/fcell.2023.1151348. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37091979 Free PMC article. Review. - (Non)Parallel developmental mechanisms in vertebrate appendage reduction and loss.
Swank S, Sanger TJ, Stuart YE. Swank S, et al. Ecol Evol. 2021 Oct 22;11(22):15484-15497. doi: 10.1002/ece3.8226. eCollection 2021 Nov. Ecol Evol. 2021. PMID: 34824770 Free PMC article. Review. - Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.
Morishita Y, Kuroiwa A, Suzuki T. Morishita Y, et al. Development. 2015 May 1;142(9):1672-83. doi: 10.1242/dev.109728. Epub 2015 Apr 9. Development. 2015. PMID: 25858459 Free PMC article. - Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties.
Long J, Tokhunts R, Old WM, Houel S, Rodgriguez-Blanco J, Singh S, Schilling N, J Capobianco A, Ahn NG, Robbins DJ. Long J, et al. Cell Rep. 2015 Mar 3;10(8):1280-1287. doi: 10.1016/j.celrep.2015.01.058. Epub 2015 Feb 26. Cell Rep. 2015. PMID: 25732819 Free PMC article. - Review of literature: genes related to postaxial polydactyly.
Verma PK, El-Harouni AA. Verma PK, et al. Front Pediatr. 2015 Feb 11;3:8. doi: 10.3389/fped.2015.00008. eCollection 2015. Front Pediatr. 2015. PMID: 25717468 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources