Knockdown of hspg2 is associated with abnormal mandibular joint formation and neural crest cell dysfunction in zebrafish
Background: Heparan sulfate proteoglycan 2 (HSPG2) encodes for perlecan, a large proteoglycan that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations in HSPG2 have been associated with Schwartz-Jampel Syndrome (SJS) and Dyssegmental Dysplasia Silverman-Handmaker Type (DDSH), two disorders characterized by skeletal abnormalities. These data indicate a function for HSPG2 in cartilage development/maintenance. However, the mechanisms in which HSPG2 regulates cartilage development are not completely understood. Here, we explored the relationship between this gene and craniofacial development through morpholino-mediated knockdown of hspg2 using zebrafish.
Results: Knockdown of hspg2 resulted in abnormal development of the mandibular jaw joint at 5 days post fertilization (DPF). We surmised that defects in mandible development were a consequence of neural crest cell (NCC) dysfunction, as these multipotent progenitors produce the cartilage of the head. Early NCC development was normal in morphant animals as measured by distal-less homeobox 2a (dlx2a) and SRY-box transcription factor 10 (sox10) expression at 1 DPF. However, subsequent analysis at later stages of development (4 DPF) revealed a decrease in the number of Sox10 + and Collagen, type II, alpha 1a (Col2a1a)+ cells within the mandibular jaw joint region of morphants relative to random control injected embryos. Concurrently, morphants showed a decreased expression of nkx3.2, a marker of jaw joint formation, at 4 DPF.
Conclusions: Collectively, these data suggest a complex role for hspg2 in jaw joint formation and late stage NCC differentiation.
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Posted 30 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 11 Nov, 2020
Received 01 Nov, 2020
Received 02 Oct, 2020
Received 01 Oct, 2020
On 23 Sep, 2020
On 15 Sep, 2020
Invitations sent on 10 Sep, 2020
On 10 Sep, 2020
On 01 Sep, 2020
On 31 Aug, 2020
On 31 Aug, 2020
On 28 Jul, 2020
Received 27 Jul, 2020
Received 23 Jul, 2020
Received 04 Jul, 2020
On 03 Jul, 2020
On 01 Jul, 2020
On 18 Jun, 2020
Invitations sent on 15 Jun, 2020
On 20 May, 2020
On 19 May, 2020
On 19 May, 2020
Knockdown of hspg2 is associated with abnormal mandibular joint formation and neural crest cell dysfunction in zebrafish
Posted 30 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 10 Dec, 2020
On 11 Nov, 2020
Received 01 Nov, 2020
Received 02 Oct, 2020
Received 01 Oct, 2020
On 23 Sep, 2020
On 15 Sep, 2020
Invitations sent on 10 Sep, 2020
On 10 Sep, 2020
On 01 Sep, 2020
On 31 Aug, 2020
On 31 Aug, 2020
On 28 Jul, 2020
Received 27 Jul, 2020
Received 23 Jul, 2020
Received 04 Jul, 2020
On 03 Jul, 2020
On 01 Jul, 2020
On 18 Jun, 2020
Invitations sent on 15 Jun, 2020
On 20 May, 2020
On 19 May, 2020
On 19 May, 2020
Background: Heparan sulfate proteoglycan 2 (HSPG2) encodes for perlecan, a large proteoglycan that plays an important role in cartilage formation, cell adhesion, and basement membrane stability. Mutations in HSPG2 have been associated with Schwartz-Jampel Syndrome (SJS) and Dyssegmental Dysplasia Silverman-Handmaker Type (DDSH), two disorders characterized by skeletal abnormalities. These data indicate a function for HSPG2 in cartilage development/maintenance. However, the mechanisms in which HSPG2 regulates cartilage development are not completely understood. Here, we explored the relationship between this gene and craniofacial development through morpholino-mediated knockdown of hspg2 using zebrafish.
Results: Knockdown of hspg2 resulted in abnormal development of the mandibular jaw joint at 5 days post fertilization (DPF). We surmised that defects in mandible development were a consequence of neural crest cell (NCC) dysfunction, as these multipotent progenitors produce the cartilage of the head. Early NCC development was normal in morphant animals as measured by distal-less homeobox 2a (dlx2a) and SRY-box transcription factor 10 (sox10) expression at 1 DPF. However, subsequent analysis at later stages of development (4 DPF) revealed a decrease in the number of Sox10 + and Collagen, type II, alpha 1a (Col2a1a)+ cells within the mandibular jaw joint region of morphants relative to random control injected embryos. Concurrently, morphants showed a decreased expression of nkx3.2, a marker of jaw joint formation, at 4 DPF.
Conclusions: Collectively, these data suggest a complex role for hspg2 in jaw joint formation and late stage NCC differentiation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7