The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform

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The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform. / Hultman, Karin; Scarlett, Jarrad M.; Baquero, Arian F.; Cornea, Anda; Zhang, Yu; Salinas, Casper B.G.; Brown, Jenny; Morton, Gregory J.; Whalen, Erin J.; Grove, Kevin L.; Koegler, Frank H.; Schwartz, Michael W.; Mercer, Aaron J.

In: Journal of Comparative Neurology, Vol. 527, No. 12, 15.08.2019, p. 2069-2085.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hultman, K, Scarlett, JM, Baquero, AF, Cornea, A, Zhang, Y, Salinas, CBG, Brown, J, Morton, GJ, Whalen, EJ, Grove, KL, Koegler, FH, Schwartz, MW & Mercer, AJ 2019, 'The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform', Journal of Comparative Neurology, vol. 527, no. 12, pp. 2069-2085. https://doi.org/10.1002/cne.24668

APA

Hultman, K., Scarlett, J. M., Baquero, A. F., Cornea, A., Zhang, Y., Salinas, C. B. G., Brown, J., Morton, G. J., Whalen, E. J., Grove, K. L., Koegler, F. H., Schwartz, M. W., & Mercer, A. J. (2019). The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform. Journal of Comparative Neurology, 527(12), 2069-2085. https://doi.org/10.1002/cne.24668

Vancouver

Hultman K, Scarlett JM, Baquero AF, Cornea A, Zhang Y, Salinas CBG et al. The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform. Journal of Comparative Neurology. 2019 Aug 15;527(12):2069-2085. https://doi.org/10.1002/cne.24668

Author

Hultman, Karin ; Scarlett, Jarrad M. ; Baquero, Arian F. ; Cornea, Anda ; Zhang, Yu ; Salinas, Casper B.G. ; Brown, Jenny ; Morton, Gregory J. ; Whalen, Erin J. ; Grove, Kevin L. ; Koegler, Frank H. ; Schwartz, Michael W. ; Mercer, Aaron J. / The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform. In: Journal of Comparative Neurology. 2019 ; Vol. 527, No. 12. pp. 2069-2085.

Bibtex

@article{671ed192aad142159cebd20081e4ddd1,
title = "The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform",
abstract = "Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models of obesity and diabetes. The current work was undertaken to advance our understanding of the receptor expression, as sites of ligand action by FGF19, FGF21, and FGF1 in the mammalian brain remains unresolved. Recent advances in automated RNAscope in situ hybridization and droplet digital PCR (ddPCR) technology allowed us to interrogate central FGFR/beta klotho (Klb) system at the cellular level in the mouse, with relevant comparisons to nonhuman primate and human brain. FGFR1-3 gene expression was broadly distributed throughout the CNS in Mus musculus, with FGFR1 exhibiting the greatest heterogeneity. FGFR4 expression localized only in the medial habenula and subcommissural organ of mice. Likewise, Klb mRNA was restricted to the suprachiasmatic nucleus (SCh) and select midbrain and hindbrain nuclei. ddPCR in the rodent hypothalamus confirmed that, although expression levels are indeed low for Klb, there is nonetheless a bonafide subpopulation of Klb+ cells in the hypothalamus. In NHP and human midbrain and hindbrain, Klb + cells are quite rare, as is expression of FGFR4. Collectively, these data provide the most robust central map of the FGFR/Klb system to date and highlight central regions that may be of critical importance to assess central ligand effects with pharmacological dosing, such as the putative interactions between the endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.",
keywords = "RRID: AB_2109645, RRID: AB_2532109, RRID: AB_839504, beta-klotho, fibroblast growth factors, in situ hybridization, obesity, type 2 diabetes",
author = "Karin Hultman and Scarlett, {Jarrad M.} and Baquero, {Arian F.} and Anda Cornea and Yu Zhang and Salinas, {Casper B.G.} and Jenny Brown and Morton, {Gregory J.} and Whalen, {Erin J.} and Grove, {Kevin L.} and Koegler, {Frank H.} and Schwartz, {Michael W.} and Mercer, {Aaron J.}",
year = "2019",
month = aug,
day = "15",
doi = "10.1002/cne.24668",
language = "English",
volume = "527",
pages = "2069--2085",
journal = "The Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "JohnWiley & Sons, Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - The central fibroblast growth factor receptor/beta klotho system: Comprehensive mapping in Mus musculus and comparisons to nonhuman primate and human samples using an automated in situ hybridization platform

AU - Hultman, Karin

AU - Scarlett, Jarrad M.

AU - Baquero, Arian F.

AU - Cornea, Anda

AU - Zhang, Yu

AU - Salinas, Casper B.G.

AU - Brown, Jenny

AU - Morton, Gregory J.

AU - Whalen, Erin J.

AU - Grove, Kevin L.

AU - Koegler, Frank H.

AU - Schwartz, Michael W.

AU - Mercer, Aaron J.

PY - 2019/8/15

Y1 - 2019/8/15

N2 - Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models of obesity and diabetes. The current work was undertaken to advance our understanding of the receptor expression, as sites of ligand action by FGF19, FGF21, and FGF1 in the mammalian brain remains unresolved. Recent advances in automated RNAscope in situ hybridization and droplet digital PCR (ddPCR) technology allowed us to interrogate central FGFR/beta klotho (Klb) system at the cellular level in the mouse, with relevant comparisons to nonhuman primate and human brain. FGFR1-3 gene expression was broadly distributed throughout the CNS in Mus musculus, with FGFR1 exhibiting the greatest heterogeneity. FGFR4 expression localized only in the medial habenula and subcommissural organ of mice. Likewise, Klb mRNA was restricted to the suprachiasmatic nucleus (SCh) and select midbrain and hindbrain nuclei. ddPCR in the rodent hypothalamus confirmed that, although expression levels are indeed low for Klb, there is nonetheless a bonafide subpopulation of Klb+ cells in the hypothalamus. In NHP and human midbrain and hindbrain, Klb + cells are quite rare, as is expression of FGFR4. Collectively, these data provide the most robust central map of the FGFR/Klb system to date and highlight central regions that may be of critical importance to assess central ligand effects with pharmacological dosing, such as the putative interactions between the endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.

AB - Central activation of fibroblast growth factor (FGF) receptors regulates peripheral glucose homeostasis and reduces food intake in preclinical models of obesity and diabetes. The current work was undertaken to advance our understanding of the receptor expression, as sites of ligand action by FGF19, FGF21, and FGF1 in the mammalian brain remains unresolved. Recent advances in automated RNAscope in situ hybridization and droplet digital PCR (ddPCR) technology allowed us to interrogate central FGFR/beta klotho (Klb) system at the cellular level in the mouse, with relevant comparisons to nonhuman primate and human brain. FGFR1-3 gene expression was broadly distributed throughout the CNS in Mus musculus, with FGFR1 exhibiting the greatest heterogeneity. FGFR4 expression localized only in the medial habenula and subcommissural organ of mice. Likewise, Klb mRNA was restricted to the suprachiasmatic nucleus (SCh) and select midbrain and hindbrain nuclei. ddPCR in the rodent hypothalamus confirmed that, although expression levels are indeed low for Klb, there is nonetheless a bonafide subpopulation of Klb+ cells in the hypothalamus. In NHP and human midbrain and hindbrain, Klb + cells are quite rare, as is expression of FGFR4. Collectively, these data provide the most robust central map of the FGFR/Klb system to date and highlight central regions that may be of critical importance to assess central ligand effects with pharmacological dosing, such as the putative interactions between the endocrine FGFs and FGFR1/Klb, or FGF19 with FGFR4.

KW - RRID: AB_2109645

KW - RRID: AB_2532109

KW - RRID: AB_839504

KW - beta-klotho

KW - fibroblast growth factors

KW - in situ hybridization

KW - obesity

KW - type 2 diabetes

UR - https://www.mendeley.com/catalogue/8d13bbbf-aef6-34e0-9fb6-e46deda96739/

U2 - 10.1002/cne.24668

DO - 10.1002/cne.24668

M3 - Journal article

C2 - 30809795

VL - 527

SP - 2069

EP - 2085

JO - The Journal of Comparative Neurology

JF - The Journal of Comparative Neurology

SN - 0021-9967

IS - 12

ER -

ID: 261001758