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Research article
Knockdown of hspg2 is associated with abnormal mandibular joint formation and neural crest cell dysfunction in zebrafish
Anita Quintana
University of Texas at El Paso
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3596-1587
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This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
HSPG2, neural crest cells, craniofacial development
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Reviewer #3 agreed
On 03 Jul, 2020
Reviewer #2 agreed
On 01 Jul, 2020
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On 18 Jun, 2020
Reviewers invited
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This preprint is under consideration at BMC Developmental Biology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Knockdown of hspg2 is associated with abnormal mandibular joint formation and neural crest cell dysfunction in zebrafish
Anita Quintana
University of Texas at El Paso
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3596-1587
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 3
Posted 30 Dec, 2020
No community comments so far
Editor assigned
On 10 Dec, 2020
Submission checks complete
On 10 Dec, 2020
Editor invited
On 10 Dec, 2020
No comments provided
Editorial decision: Major revision
On 11 Nov, 2020
Review #3 received
Received 01 Nov, 2020
Review #2 received
Received 02 Oct, 2020
Review #1 received
Received 01 Oct, 2020
Reviewer #3 agreed
On 23 Sep, 2020
Reviewer #2 agreed
On 15 Sep, 2020
Reviewers invited
Invitations sent on 10 Sep, 2020
Reviewer #1 agreed
On 10 Sep, 2020
Editor assigned
On 01 Sep, 2020
Submission checks complete
On 31 Aug, 2020
Editor invited
On 31 Aug, 2020
No comments provided
Editorial decision: Major revision
On 28 Jul, 2020
Review #2 received
Received 27 Jul, 2020
Review #3 received
Received 23 Jul, 2020
Review #1 received
Received 04 Jul, 2020
Reviewer #3 agreed
On 03 Jul, 2020
Reviewer #2 agreed
On 01 Jul, 2020
Reviewer #1 agreed
On 18 Jun, 2020
Reviewers invited
Invitations sent on 15 Jun, 2020
Editor assigned
On 20 May, 2020
Submission checks complete
On 19 May, 2020
Editor invited
On 19 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Developmental Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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