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Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian development in a marsupial.

O'Hara WA, Azar WJ, Behringer RR, Renfree MB, Pask AJ - BMC Dev. Biol. (2011)

Bottom Line: Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1.The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads.Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis.

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Affiliation: Department of Molecular and Cellular Biology, The University of Connecticut, Storrs, CT 06269, USA.

ABSTRACT

Background: Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals.

Results: DHH, PTCH1 and PTCH2 were present in the marsupial genome and highly conserved with their eutherian orthologues. Phylogenetic analyses indicate that DHH has recently evolved and is a mammal-specific hedgehog orthologue. The marsupial PTCH2 receptor had an additional exon (exon 21a) not annotated in eutherian PTCH2 proteins. Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1. We also show that DHH expression was not restricted to the testes during gonadal development (as in mice), but was also expressed in the developing ovary. Expression of DHH, PTCH1 and PTCH2 in the adult tammar testis and ovary was consistent with findings in the adult mouse.

Conclusions: These data suggest that there is a highly conserved role for DHH signalling in the differentiation and function of the mammalian testis and that DHH may be necessary for marsupial ovarian development. The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads. Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis.

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Immunohistochemistry of DHH, PTCH1 and PTCH2 in the tammar wallaby testis at key developmental time points. Red/brown staining indicates protein distribution while the heamatoxalin counterstain appears blue. It is important to note that DHH is a highly secreted molecule and staining does not imply cell of origin. DHH staining was most intense at the basal lamina (BL). In the adult staining is concentrated in the develop spermatocytes (GC). At day D9pp PTCH1 was present within the Sertoli cells (SC) while PTCH2 was predominant in the Leydig cells (LC). This expression profile is reversed in the adult testis with PTCH1 found predominantly in the Leydig cells, while PTCH2 was predominate in the Sertoli cells. Scale bars indicate 40 μm, controls show immunohistochemistry with the primary antibody omitted.
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Figure 5: Immunohistochemistry of DHH, PTCH1 and PTCH2 in the tammar wallaby testis at key developmental time points. Red/brown staining indicates protein distribution while the heamatoxalin counterstain appears blue. It is important to note that DHH is a highly secreted molecule and staining does not imply cell of origin. DHH staining was most intense at the basal lamina (BL). In the adult staining is concentrated in the develop spermatocytes (GC). At day D9pp PTCH1 was present within the Sertoli cells (SC) while PTCH2 was predominant in the Leydig cells (LC). This expression profile is reversed in the adult testis with PTCH1 found predominantly in the Leydig cells, while PTCH2 was predominate in the Sertoli cells. Scale bars indicate 40 μm, controls show immunohistochemistry with the primary antibody omitted.

Mentions: DHH was widely distributed throughout the bipotential gonad, PTCH1 and 2 staining was present but very weak (Additional file 9, d24 fetus). By day 1 pp the cords were beginning to form in the testis, and DHH stained pre-Sertoli cells that were coalescing into cord- like structures (Additional file 9, D1pp). PTCH1 protein stained weakly throughout the gonad while PTCH2 appeared more prominent and was localized outside the forming cords. At day 9 pp cords were fully formed in the developing testis. DHH protein was present throughout the gonad and was strongly detected in some Sertoli cells and in the peritubular myoid cells and at the basement membrane. PTCH1 was diffuse throughout the gonad but was mainly localised in the Sertoli cells and absent from the interstitium. Conversely, PTCH2 staining was more intense and concentrated in Leydig cells in the interstitium (Figure 5). In the adult testis, DHH was present at low levels in all cell types, but strong staining was seen in round spermatids from the post pachytene primary spermatocyte stage, through to the mature sperm. PTCH1 was present at high levels in the Leydig cells and showed a punctate distribution reminiscent of membrane bound protein recycling [46]. PTCH2 distribution also became highly restricted and localised strongly in the Sertoli cells (Figure 5).


Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian development in a marsupial.

O'Hara WA, Azar WJ, Behringer RR, Renfree MB, Pask AJ - BMC Dev. Biol. (2011)

Immunohistochemistry of DHH, PTCH1 and PTCH2 in the tammar wallaby testis at key developmental time points. Red/brown staining indicates protein distribution while the heamatoxalin counterstain appears blue. It is important to note that DHH is a highly secreted molecule and staining does not imply cell of origin. DHH staining was most intense at the basal lamina (BL). In the adult staining is concentrated in the develop spermatocytes (GC). At day D9pp PTCH1 was present within the Sertoli cells (SC) while PTCH2 was predominant in the Leydig cells (LC). This expression profile is reversed in the adult testis with PTCH1 found predominantly in the Leydig cells, while PTCH2 was predominate in the Sertoli cells. Scale bars indicate 40 μm, controls show immunohistochemistry with the primary antibody omitted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3293750&req=5

Figure 5: Immunohistochemistry of DHH, PTCH1 and PTCH2 in the tammar wallaby testis at key developmental time points. Red/brown staining indicates protein distribution while the heamatoxalin counterstain appears blue. It is important to note that DHH is a highly secreted molecule and staining does not imply cell of origin. DHH staining was most intense at the basal lamina (BL). In the adult staining is concentrated in the develop spermatocytes (GC). At day D9pp PTCH1 was present within the Sertoli cells (SC) while PTCH2 was predominant in the Leydig cells (LC). This expression profile is reversed in the adult testis with PTCH1 found predominantly in the Leydig cells, while PTCH2 was predominate in the Sertoli cells. Scale bars indicate 40 μm, controls show immunohistochemistry with the primary antibody omitted.
Mentions: DHH was widely distributed throughout the bipotential gonad, PTCH1 and 2 staining was present but very weak (Additional file 9, d24 fetus). By day 1 pp the cords were beginning to form in the testis, and DHH stained pre-Sertoli cells that were coalescing into cord- like structures (Additional file 9, D1pp). PTCH1 protein stained weakly throughout the gonad while PTCH2 appeared more prominent and was localized outside the forming cords. At day 9 pp cords were fully formed in the developing testis. DHH protein was present throughout the gonad and was strongly detected in some Sertoli cells and in the peritubular myoid cells and at the basement membrane. PTCH1 was diffuse throughout the gonad but was mainly localised in the Sertoli cells and absent from the interstitium. Conversely, PTCH2 staining was more intense and concentrated in Leydig cells in the interstitium (Figure 5). In the adult testis, DHH was present at low levels in all cell types, but strong staining was seen in round spermatids from the post pachytene primary spermatocyte stage, through to the mature sperm. PTCH1 was present at high levels in the Leydig cells and showed a punctate distribution reminiscent of membrane bound protein recycling [46]. PTCH2 distribution also became highly restricted and localised strongly in the Sertoli cells (Figure 5).

Bottom Line: Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1.The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads.Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Biology, The University of Connecticut, Storrs, CT 06269, USA.

ABSTRACT

Background: Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals.

Results: DHH, PTCH1 and PTCH2 were present in the marsupial genome and highly conserved with their eutherian orthologues. Phylogenetic analyses indicate that DHH has recently evolved and is a mammal-specific hedgehog orthologue. The marsupial PTCH2 receptor had an additional exon (exon 21a) not annotated in eutherian PTCH2 proteins. Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1. We also show that DHH expression was not restricted to the testes during gonadal development (as in mice), but was also expressed in the developing ovary. Expression of DHH, PTCH1 and PTCH2 in the adult tammar testis and ovary was consistent with findings in the adult mouse.

Conclusions: These data suggest that there is a highly conserved role for DHH signalling in the differentiation and function of the mammalian testis and that DHH may be necessary for marsupial ovarian development. The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads. Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis.

Show MeSH
Related in: MedlinePlus