Hippo signaling instructs ectopic but not normal organ growth

Kowalczyk, Weronika; Romanelli, Lucia; Atkins, Mardelle; Hillen, Hanne; González-Blas, Carmen Bravo; Jacobs, Jelle; Xie, Jun; Soheily, Soheil; Verboven, Elisabeth; Moya, Iván M.; Verhulst, Stefaan; Sansores-García, Leticia; Huffel, Leen Van; Johnson, Randy L.; Grunsven, Leo A. van; Aerts, Stein; Halder, Georg

doi:10.1126/science.abg3679

Cited by 45 publications

(51 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Figure 3H, Y_1 cells shared an expression profile similar to that of the VPE and INT. This similarity to peripodial membrane cells of the VPE is in line with previous work which suggests that Yki is primarily active in cells of the peripodial membrane 39 . Importantly, the Y_1 transcriptional profile most closely resembled wild type interommatidial cells INT, but showed no similarity to anterior cell populations.…”

Section: Ectopic Expression Of Constitutively Activated Yki In Rbf Mu...supporting

confidence: 91%

Combined inactivation of RB and Hippo pathways converts differentiating photoreceptors into eye progenitor cells through derepression ofhomothorax

Bayarmagnai

Frolov

2023

Preprint

View full text Add to dashboard Cite

The RB and Hippo pathways interact to regulate cell proliferation and differentiation. However, their mechanism of interaction is not fully understood. Drosophila photoreceptors with inactivated RB and Hippo pathways specify normally but fail to maintain neuronal identity and dedifferentiate. We performed single-cell RNA-sequencing to elucidate the cause of dedifferentiation and the fate of these cells. We find that dedifferentiated cells adopt a progenitor-like fate due to inappropriate activation of the retinal differentiation suppressor homothorax (hth) by Yki/Sd. This results in activation of the Yki/Hth transcriptional program, driving photoreceptor dedifferentiation. We show that Rbf physically interacts with Yki which, together with the GAGA factor, inhibits hth expression. Thus, RB and Hippo pathways cooperate to maintain photoreceptor differentiation by preventing inappropriate expression of hth in differentiating photoreceptors. Our work accentuates the importance of both RB and Hippo pathway activity for maintaining the state of terminal differentiation.

show abstract

Section: Ectopic Expression Of Constitutively Activated Yki In Rbf Mu...supporting

confidence: 91%

Combined inactivation of RB and Hippo pathways converts differentiating photoreceptors into eye progenitor cells through derepression ofhomothorax

Bayarmagnai

Frolov

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Similarly, we mapped an Yki signature gene set composed of 52 genes to our data (18) (Supplemental Table 3) and found that the scrib -/-Yki S168A clones exhibit higher expression level of Yki target genes in comparison with GFP-cells (Figure 1J'). The scrib -/-N Act clones express higher level of the enhancer of split gene complex, which are well-known Notch signaling targets (19) (Figure 1K').…”

Section: Resultsmentioning

confidence: 91%

Oncogenic Ras, Yki and Notch signals converge to confer clone competitiveness through Upd2

Wang

Deng

et al. 2023

Preprint

View full text Add to dashboard Cite

It has long been proposed that cell competition functions to remove precancerous clones. A classical model is the removal of polarity-deficient clones such as the scribble (scrib) mutant clones in Drosophila imaginal discs. The activation of Ras, Yki or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth. Using single-cell transcriptomics techniques to profile wing imaginal discs harboring the scrib mutant clones in combination with different signals, we found that a critical converging point downstream of Ras, Yki and Notch signals is the upregulation of Upd2, which is necessary to promote tumorous growth. Unexpectedly, while Upd2 is not required for cell survival per se, Upd2-deficient clones are efficiently wiped out from epithelia, indicating that Upd2 is a previously unrecognized cell competition factor.

show abstract

“…In the absence of Yki, Sd binds to repressors and is thought to reduce expression of target genes (Guo et al, 2013; Koontz et al, 2013). Loss of sd causes the loss of both its activator and repressor functions and, in many contexts, results in relatively minor changes in tissue size (Goulev et al, 2008; Wu et al, 2008; Zhang et al, 2008; Kowalczyk et al, 2022). Although sd null clones fail to grow in the PE of the eye disc (Kowalczyk et al, 2022), and Yki/Sd-mediated cell proliferation promotes stretch-induced growth of the egg follicle epithelium (Borreguero-Muñoz et al, 2019), the frequent lack of a strong growth phenotype upon sd loss has placed into question whether the Hippo pathway plays a significant role in size regulation during normal development (Kowalczyk et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

Coordinated growth of linked epithelia is mediated by the Hippo pathway

Friesen

Hariharan

2023

Preprint

View full text Add to dashboard Cite

An epithelium in a living organism seldom develops in isolation. Rather, most epithelia are tethered to other epithelial or non-epithelial tissues, necessitating growth coordination between layers. We investigated how two tethered epithelial layers of theDrosophilalarval wing imaginal disc, the disc proper (DP) and the peripodial epithelium (PE), coordinate their growth. DP growth is driven by the morphogens Hedgehog (Hh) and Dpp, but regulation of PE growth is poorly understood. We find that the PE adapts to changes in growth rates of the DP, but not vice versa, thus favoring a leader and follower mechanism. Moreover, PE growth can occur by cell shape changes, even when proliferation is inhibited. While Hh and Dpp pattern gene expression in both layers, growth of the DP is exquisitely sensitive to Dpp levels, while growth of the PE is not; the PE can achieve an appropriate size even when Dpp signaling is inhibited. Instead, both the growth of the PE and its accompanying cell shape changes require the activity of two components of the mechanosensitive Hippo pathway, the DNA-binding protein Scalloped (Sd) and its co-activator (Yki), which could allow the PE to sense and respond to forces generated by DP growth. Thus, an increased reliance on mechanically-dependent growth mediated by the Hippo pathway, at the expense of morphogen-dependent growth, enables the PE to evade layer-intrinsic growth control mechanisms and coordinate its growth with the DP. This provides a potential paradigm for growth coordination between different components of a developing organ.

show abstract

Hippo signaling instructs ectopic but not normal organ growth

Cited by 45 publications

References 80 publications

Combined inactivation of RB and Hippo pathways converts differentiating photoreceptors into eye progenitor cells through derepression ofhomothorax

Combined inactivation of RB and Hippo pathways converts differentiating photoreceptors into eye progenitor cells through derepression ofhomothorax

Oncogenic Ras, Yki and Notch signals converge to confer clone competitiveness through Upd2

Coordinated growth of linked epithelia is mediated by the Hippo pathway

Contact Info

Product

Resources

About